The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.
The use of computers for designing and/or manufacturing of anything, including drugs, surgical procedures, orthotics, and prosthetics.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
A quantitative prediction of the biological, ecotoxicological or pharmaceutical activity of a molecule. It is based upon structure and activity information gathered from a series of similar compounds.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
The process of finding chemicals for potential therapeutic use.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly.
Amino acid sequence in which two disulfide bonds (DISULFIDES) and their connecting backbone form a ring that is penetrated by a third disulfide bond. Members include CYCLOTIDES and agouti-related protein.
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
The characteristic three-dimensional shape of a molecule.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A computer simulation developed to study the motion of molecules over a period of time.
A structurally-related family of small proteins that form a stable tertiary fold pattern which is supported by a series of disulfide bonds. The arrangement of disulfide bonds between the CYSTEINE moieties results in a knotted structure which is unique to this family of proteins.
The degree of 3-dimensional shape similarity between proteins. It can be an indication of distant AMINO ACID SEQUENCE HOMOLOGY and used for rational DRUG DESIGN.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.
Computer-based representation of physical systems and phenomena such as chemical processes.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions.
A continuous circle of peptide bonds, typically of 2-3 dozen AMINO ACIDS, so there is no free N- or C-terminus. They are further characterized by six conserved CYSTEINE residues that form CYSTINE KNOT MOTIFS.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.
A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.
A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.
Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.
A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)
Sequential operating programs and data which instruct the functioning of a digital computer.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Databases devoted to knowledge about PHARMACEUTICAL PRODUCTS.
Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.
Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.
Methods of creating machines and devices.
Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use.
The collective name for the boron hydrides, which are analogous to the alkanes and silanes. Numerous boranes are known. Some have high calorific values and are used in high-energy fuels. (From Grant & Hackh's Chemical Dictionary, 5th ed)
Dioxygenases that catalyze the peroxidation of methylene-interrupted UNSATURATED FATTY ACIDS.
The field of information science concerned with the analysis and dissemination of data through the application of computers.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A class of organic compounds containing two ring structures, one of which is made up of more than one kind of atom, usually carbon plus another atom. The heterocycle may be either aromatic or nonaromatic.
The formation of crystalline substances from solutions or melts. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.
NMR spectroscopy on small- to medium-size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope.
Inorganic derivatives of phosphorus trihydroxide (P(OH)3) and its tautomeric form dihydroxyphosphine oxide (HP=O(OH)2). Note that organic derivatives of phosphonic acids are listed under are ORGANOPHOSPHONATES.
Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Inhibitors of HIV INTEGRASE, an enzyme required for integration of viral DNA into cellular DNA.
The portion of an interactive computer program that issues messages to and receives commands from a user.
Rapid methods of measuring the effects of an agent in a biological or chemical assay. The assay usually involves some form of automation or a way to conduct multiple assays at the same time using sample arrays.
The thermodynamic interaction between a substance and WATER.
Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).
Protein modules with conserved ligand-binding surfaces which mediate specific interaction functions in SIGNAL TRANSDUCTION PATHWAYS and the specific BINDING SITES of their cognate protein LIGANDS.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes.
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
A technology, in which sets of reactions for solution or solid-phase synthesis, is used to create molecular libraries for analysis of compounds on a large scale.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Methods for determining interaction between PROTEINS.
A site on an enzyme which upon binding of a modulator, causes the enzyme to undergo a conformational change that may alter its catalytic or binding properties.
The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).
The rate dynamics in chemical or physical systems.
The accumulation of an electric charge on a object
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
Biological molecules that possess catalytic activity. They may occur naturally or be synthetically created. Enzymes are usually proteins, however CATALYTIC RNA and CATALYTIC DNA molecules have also been identified.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
Extensive collections, reputedly complete, of facts and data garnered from material of a specialized subject area and made available for analysis and application. The collection can be automated by various contemporary methods for retrieval. The concept should be differentiated from DATABASES, BIBLIOGRAPHIC which is restricted to collections of bibliographic references.
The quality or state of being able to be bent or creased repeatedly. (From Webster, 3d ed)
Agents destructive to the protozoal organisms belonging to the suborder TRYPANOSOMATINA.
The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Higher-order DNA and RNA structures formed from guanine-rich sequences. They are formed around a core of at least 2 stacked tetrads of hydrogen-bonded GUANINE bases. They can be formed from one two or four separate strands of DNA (or RNA) and can display a wide variety of topologies, which are a consequence of various combinations of strand direction, length, and sequence. (From Nucleic Acids Res. 2006;34(19):5402-15)
Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.
The measure of that part of the heat or energy of a system which is not available to perform work. Entropy increases in all natural (spontaneous and irreversible) processes. (From Dorland, 28th ed)
Liquids that dissolve other substances (solutes), generally solids, without any change in chemical composition, as, water containing sugar. (Grant & Hackh's Chemical Dictionary, 5th ed)
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
The measurement of the quantity of heat involved in various processes, such as chemical reactions, changes of state, and formations of solutions, or in the determination of the heat capacities of substances. The fundamental unit of measurement is the joule or the calorie (4.184 joules). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Proteins prepared by recombinant DNA technology.
Agents that inhibit PROTEIN KINASES.
Learning algorithms which are a set of related supervised computer learning methods that analyze data and recognize patterns, and used for classification and regression analysis.
The branch of science that deals with the geometric description of crystals and their internal arrangement. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Drugs used to treat or prevent parasitic infections.
Inorganic or organic oxy acids of sulfur which contain the RSO2(OH) radical.
The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Substances that are destructive to protozoans.
The homogeneous mixtures formed by the mixing of a solid, liquid, or gaseous substance (solute) with a liquid (the solvent), from which the dissolved substances can be recovered by physical processes. (From Grant & Hackh's Chemical Dictionary, 5th ed)
An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992)
Peptides composed of between two and twelve amino acids.
The agent of South American trypanosomiasis or CHAGAS DISEASE. Its vertebrate hosts are man and various domestic and wild animals. Insects of several species are vectors.
Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease.
The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.
The application of scientific knowledge or technology to pharmacy and the pharmaceutical industry. It includes methods, techniques, and instrumentation in the manufacture, preparation, compounding, dispensing, packaging, and storing of drugs and other preparations used in diagnostic and determinative procedures, and in the treatment of patients.
Elements of limited time intervals, contributing to particular results or situations.
Enzyme of the HUMAN IMMUNODEFICIENCY VIRUS that is required to integrate viral DNA into cellular DNA in the nucleus of a host cell. HIV integrase is a DNA nucleotidyltransferase encoded by the pol gene.
The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
The theory that the radiation and absorption of energy take place in definite quantities called quanta (E) which vary in size and are defined by the equation E=hv in which h is Planck's constant and v is the frequency of the radiation.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.
The process by which two molecules of the same chemical composition form a condensation product or polymer.
Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)
The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
The plan and delineation of prostheses in general or a specific prosthesis.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
That segment of commercial enterprise devoted to the design, development, and manufacture of chemical products for use in the diagnosis and treatment of disease, disability, or other dysfunction, or to improve function.
The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.
The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Proteins found in any species of bacterium.
Complex pharmaceutical substances, preparations, or matter derived from organisms usually obtained by biological methods or assay.
Specifications and instructions applied to the software.
A cell line derived from cultured tumor cells.
Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)
Theory and development of COMPUTER SYSTEMS which perform tasks that normally require human intelligence. Such tasks may include speech recognition, LEARNING; VISUAL PERCEPTION; MATHEMATICAL COMPUTING; reasoning, PROBLEM SOLVING, DECISION-MAKING, and translation of language.
A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.
Proteins found in any species of protozoan.
An enzyme of the transferase class that catalyzes the reaction 5,10-methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).

Melanoma cells present a MAGE-3 epitope to CD4(+) cytotoxic T cells in association with histocompatibility leukocyte antigen DR11. (1/5661)

In this study we used TEPITOPE, a new epitope prediction software, to identify sequence segments on the MAGE-3 protein with promiscuous binding to histocompatibility leukocyte antigen (HLA)-DR molecules. Synthetic peptides corresponding to the identified sequences were synthesized and used to propagate CD4(+) T cells from the blood of a healthy donor. CD4(+) T cells strongly recognized MAGE-3281-295 and, to a lesser extent, MAGE-3141-155 and MAGE-3146-160. Moreover, CD4(+) T cells proliferated in the presence of recombinant MAGE-3 after processing and presentation by autologous antigen presenting cells, demonstrating that the MAGE-3 epitopes recognized are naturally processed. CD4(+) T cells, mostly of the T helper 1 type, showed specific lytic activity against HLA-DR11/MAGE-3-positive melanoma cells. Cold target inhibition experiments demonstrated indeed that the CD4(+) T cells recognized MAGE-3281-295 in association with HLA-DR11 on melanoma cells. This is the first evidence that a tumor-specific shared antigen forms CD4(+) T cell epitopes. Furthermore, we validated the use of algorithms for the prediction of promiscuous CD4(+) T cell epitopes, thus opening the possibility of wide application to other tumor-associated antigens. These results have direct implications for cancer immunotherapy in the design of peptide-based vaccines with tumor-specific CD4(+) T cell epitopes.  (+info)

Disorders in cell circuitry associated with multistage carcinogenesis: exploitable targets for cancer prevention and therapy. (2/5661)

The development of a malignant tumor involves the progressive acquisition of mutations and epigenetic abnormalities in multiple genes that have highly diverse functions. Some of these genes code for pathways of signal transduction that mediate the action of growth factors. The enzyme protein kinase C plays an important role in these events and in the process of tumor promotion. Therefore, we examined the effects of three inhibitors of protein kinase C, CGP 41251, RO 31-8220, and calphostin C, on human glioblastoma cells. These compounds inhibited growth and induced apoptosis; these activities were associated with a decrease in the level of CDC2 and cyclin B1/CDC2-associated kinase activity. This may explain why the treated cells accumulated in G2-M. In a separate series of studies, we examined abnormalities in cell cycle control genes in human cancer. We have found that cyclin D1 is frequently overexpressed in a variety of human cancers. Mechanistic studies indicate that cyclin D1 can play a critical role in carcinogenesis because: overexpression enhances cell transformation and tumorigenesis; introduction of an antisense cyclin D1 cDNA into either human esophageal or colon cancer cells reverts their malignant phenotype; and overexpression of cyclin D1 can enhance the amplification of other genes. The latter finding suggests that cyclin D1 can enhance genomic instability and, thereby, the process of tumor progression. Therefore, inhibitors of the function of cyclin D1 may be useful in both cancer chemoprevention and therapy. We obtained evidence for the existence of homeostatic feedback loops between cyclins D1 or E and the cell cycle inhibitory protein p27Kip1. On the basis of these and other findings, we hypothesize that, because of their disordered circuitry, cancer cells suffer from "gene addiction" and "gene hypersensitivity," disorders that might be exploited in both cancer prevention and therapy.  (+info)

Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice. (3/5661)

Cathepsins have been implicated in the degradation of proteins destined for the MHC class II processing pathway and in the proteolytic removal of invariant chain (Ii), a critical regulator of MHC class II function. Mice lacking the lysosomal cysteine proteinase cathepsin S (catS) demonstrated a profound inhibition of Ii degradation in professional APC in vivo. A marked variation in the generation of MHC class II-bound Ii fragments and presentation of exogenous proteins was observed between B cells, dendritic cells, and macrophages lacking catS. CatS-deficient mice showed diminished susceptibility to collagen-induced arthritis, suggesting a potential therapeutic target for regulation of immune responsiveness.  (+info)

A transfection compound series based on a versatile Tris linkage. (4/5661)

The family of cationic lipid transfection reagents described here demonstrates a modular design that offers potential for the ready synthesis of a wide variety of molecular variants. The key feature of these new molecules is the use of Tris as a linker for joining the hydrophobic domain to a cationic head group. The molecular design offers the opportunity to conveniently synthesise compounds differing in charge, the number and nature of hydrophobic groups in the hydrophobic domain and the characteristics of the spacer between the cationic and hydrophobic moieties. We show that prototype reagents of this design can deliver reporter genes into cultured cells with efficiencies rivaling those of established cationic lipid transfection reagents. A feature of these reagents is that they are not dependent on formulation with a neutral lipid for activity.  (+info)

Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide]. (5/5661)

In a systematic effort to design potent inhibitors of the anti-apoptotic tyrosine kinase BTK (Bruton's tyrosine kinase) as anti-leukemic agents with apoptosis-promoting and chemosensitizing properties, we have constructed a three-dimensional homology model of the BTK kinase domain. Our modeling studies revealed a distinct rectangular binding pocket near the hinge region of the BTK kinase domain with Leu460, Tyr476, Arg525, and Asp539 residues occupying the corners of the rectangle. The dimensions of this rectangle are approximately 18 x 8 x 9 x 17 A, and the thickness of the pocket is approximately 7 A. Advanced docking procedures were employed for the rational design of leflunomide metabolite (LFM) analogs with a high likelihood to bind favorably to the catalytic site within the kinase domain of BTK. The lead compound LFM-A13, for which we calculated a Ki value of 1.4 microM, inhibited human BTK in vitro with an IC50 value of 17.2 +/- 0.8 microM. Similarly, LFM-A13 inhibited recombinant BTK expressed in a baculovirus expression vector system with an IC50 value of 2.5 microM. The energetically favorable position of LFM-A13 in the binding pocket is such that its aromatic ring is close to Tyr476, and its substituent group is sandwiched between residues Arg525 and Asp539. In addition, LFM-A13 is capable of favorable hydrogen bonding interactions with BTK via Asp539 and Arg525 residues. Besides its remarkable potency in BTK kinase assays, LFM-A13 was also discovered to be a highly specific inhibitor of BTK. Even at concentrations as high as 100 micrograms/ml (approximately 278 microM), this novel inhibitor did not affect the enzymatic activity of other protein tyrosine kinases, including JAK1, JAK3, HCK, epidermal growth factor receptor kinase, and insulin receptor kinase. In accordance with the anti-apoptotic function of BTK, treatment of BTK+ B-lineage leukemic cells with LFM-A13 enhanced their sensitivity to ceramide- or vincristine-induced apoptosis. To our knowledge, LFM-A13 is the first BTK-specific tyrosine kinase inhibitor and the first anti-leukemic agent targeting BTK.  (+info)

Design of highly specific cytotoxins by using trans-splicing ribozymes. (6/5661)

We have designed ribozymes based on a self-splicing group I intron that can trans-splice exon sequences into a chosen RNA target to create a functional chimeric mRNA and provide a highly specific trigger for gene expression. We have targeted ribozymes against the coat protein mRNA of a widespread plant pathogen, cucumber mosaic virus. The ribozymes were designed to trans-splice the coding sequence of the diphtheria toxin A chain in frame with the viral initiation codon of the target sequence. Diphtheria toxin A chain catalyzes the ADP ribosylation of elongation factor 2 and can cause the cessation of protein translation. In a Saccharomyces cerevisiae model system, ribozyme expression was shown to specifically inhibit the growth of cells expressing the virus mRNA. A point mutation at the target splice site alleviated this ribozyme-mediated toxicity. Increasing the extent of base pairing between the ribozyme and target dramatically increased specific expression of the cytotoxin and reduced illegitimate toxicity in vivo. Trans-splicing ribozymes may provide a new class of agents for engineering virus resistance and therapeutic cytotoxins.  (+info)

A cytosine analog that confers enhanced potency to antisense oligonucleotides. (7/5661)

Antisense technology is based on the ability to design potent, sequence-specific inhibitors. The G-clamp heterocycle modification, a cytosine analog that clamps on to guanine by forming an additional hydrogen bond, was rationally designed to enhance oligonucleotide/RNA hybrid affinity. A single, context-dependent substitution of a G-clamp heterocycle into a 15-mer phosphorothioate oligodeoxynucleotide (S-ON) targeting the cyclin-dependent kinase inhibitor, p27(kip1), enhanced antisense activity as compared with a previously optimized C5-propynyl-modified p27(kip1) S-ON and functionally replaced 11 C5-propynyl modifications. Dose-dependent, sequence-specific antisense inhibition was observed at nanomolar concentrations of the G-clamp S-ONs. A single nucleotide mismatch between the G-clamp S-ON and the p27(kip1) mRNA reduced the potency of the antisense ON by five-fold. A 2-base-mismatch S-ON eliminated antisense activity, confirming the sequence specificity of G-clamp-modified S-ONs. The G-clamp-substituted p27(kip1) S-ON activated RNase H-mediated cleavage and demonstrated increased in vitro binding affinity for its RNA target compared with conventional 15-mer S-ONs. Furthermore, incorporation of a single G-clamp modification into a previously optimized 20-mer phosphorothioate antisense S-ON targeting c-raf increased the potency of the S-ON 25-fold. The G-clamp heterocycle is a potent, mismatch-sensitive, automated synthesizer-compatible antisense S-ON modification that will have important applications in the elucidation of gene function, the validation of gene targets, and the development of more potent antisense-based pharmaceuticals.  (+info)

Crystal structure of human type II inosine monophosphate dehydrogenase: implications for ligand binding and drug design. (8/5661)

Inosine monophosphate dehydrogenase (IMPDH) controls a key metabolic step in the regulation of cell growth and differentiation. This step is the NAD-dependent oxidation of inosine 5' monophosphate (IMP) to xanthosine 5' monophosphate, the rate-limiting step in the synthesis of the guanine nucleotides. Two isoforms of IMPDH have been identified, one of which (type II) is significantly up- regulated in neoplastic and differentiating cells. As such, it has been identified as a major target in antitumor and immunosuppressive drug design. We present here the 2.9-A structure of a ternary complex of the human type II isoform of IMPDH. The complex contains the substrate analogue 6-chloropurine riboside 5'-monophosphate (6-Cl-IMP) and the NAD analogue selenazole-4-carboxamide adenine dinucleotide, the selenium derivative of the active metabolite of the antitumor drug tiazofurin. The enzyme forms a homotetramer, with the dinucleotide binding at the monomer-monomer interface. The 6 chloro-substituted purine base is dehalogenated, forming a covalent adduct at C6 with Cys-331. The dinucleotide selenazole base is stacked against the 6-Cl-IMP purine ring in an orientation consistent with the B-side stereochemistry of hydride transfer seen with NAD. The adenosine end of the ligand interacts with residues not conserved between the type I and type II isoforms, suggesting strategies for the design of isoform-specific agents.  (+info)

Protein structure-based drug design has been contributing to the drug discovery process since the early 1990s. Structural knowledge on the exact interactions of drugs with their target proteins has been applied mainly to predict potency changes of chemically modified lead compounds.. With the 3D-structural information available today, additional aspects of the drug discovery process become predictable. Target-based virtual screening is being applied to identify new unexpected lead structures. Selectivity of compounds between homologous or orthologous proteins can be predicted, offering new possibilities to design selective compounds or predict the suitability of animal models for pharmacodynamic studies. Also the number of x-ray structures of proteins relevant for ADMET properties of drug molecules has remarkably increased during the last few years. This development offers the possibility to modulate or rationally design out unwanted ADMET properties. This covers aspects such as plasma protein ...
Title:Fragment Based Drug Design: From Experimental to Computational Approaches. VOLUME: 19 ISSUE: 30. Author(s):A. Kumar, A. Voet and K.Y.J. Zhang. Affiliation:Zhang Initiative Research Unit, Advanced Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.. Keywords:Computational fragment based drug design, de novo design, fragment based drug design, fragment growing, fragment linking, ligand efficiency, molecular docking, scaffold based drug design, protein-protein interactions, small molecule protein-protein interaction inhibitors. Abstract:Fragment based drug design has emerged as an effective alternative to high throughput screening for the identification of lead compounds in drug discovery in the past fifteen years. Fragment based screening and optimization methods have achieved credible success in many drug discovery projects with one approved drug and many more compounds in clinical trials. The fragment based drug design starts with the identification of fragments or low ...
Frontiers in Drug Design and Discovery is a book series devoted to publishing the latest and the most important advances in drug design and discovery. Eminent scientists have contributed chapters focused on all areas of rational drug design and drug discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. This book series should prove to be of interest to all pharmaceutical scientists who are involved in research in drug design and discovery and who wish to keep abreast of rapid and important developments in the field ...
Frontiers in Drug Design and Discovery is a book series devoted to publishing the latest and the most important advances in drug design and discovery. Eminent scientists have contributed chapters focused on all areas of rational drug design and drug discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. This book series should prove to be of interest to all pharmaceutical scientists who are involved in research in drug design and discovery and who wish to keep abreast of rapid and important developments in the field ...
Clinical drug development in epilepsy is characterized by a succession of trials with the principal aim of bringing a new compound to market. This article reviews the development process from first human exposure through regulatory approval to postmarketing evaluation. The basic principles of clinical trial design are examined and their application - in Phase I studies in healthy volunteers and in Phase II and Phase III studies in epilepsy patients - discussed. Monotherapy studies, the differing requirements of individual regulatory authorities, and the limitations of antiepileptic drug trials - particularly with regard to their ability to inform everyday clinical practice - are also considered. ...
Frontiers in Anti-Cancer Drug Discovery is an Ebook series devoted to publishing the latest and the most important advances in Anti-Cancer drug design and discovery. Eminent scientists write contributions on all areas of rational drug design and drug discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, recent important patents, and structure-activity relationships. The Ebook series should prove to be of interest to all pharmaceutical scientists involved in research in Anti-Cancer drug design and discovery. Each volume is devoted to the major advances in Anti-Cancer drug design and discovery. The Ebook series is essential reading to all scientists involved in drug design and discovery who wish to keep abreast of rapid and important developments in the field. The fifth volume of the series features chapters on the following topics: -Nutraceuticals and natural food products for cancer treatment -Pharmacogenomics in ...
The Action will pave the way for the development of novel drugs to treat neglected diseases such as African sleeping sickness, Chagas disease and Leishmaniasis. Related approaches of molecular genetics, biochemistry, medicinal chemistry, crystallography and bioinformatics will be coordinated and complemented with industrial experience. Established genomes are used to identify drug targets essential to the parasites but absent or different in the host, since inhibitors thereof hold promise as safe and efficacious therapeutics. Validated drug targets will serve as tools in drug discovery processes using complementary strategies: i) high-throughput screening of natural product and other compound libraries and ii) in silico screening of virtual libraries to identify novel leads; iii) chemical synthesis and optimization of identified leads; and iv) structure-based inhibitor design based on established structures or molecular models. The potential therapeutic profile of novel compounds active in vitro ...
This book is an overview of current progress in drug design, applications of drug design, and new methodologies. It focuses on energetics of drug interactions with solvents and biomolecules, applications of traditional drug design methods, and related evolutionary algorithms. The volume concludes with a survey of recent successes and failures and describes outlooks for the future.
The Tele-Intensive Care Unit market revenue was xx Million USD in 2016, grew to xx Million USD in 2020, and will reach xx Million USD in 2026, with a CAGR of xx during 2020-2026. Global Tele-Intensive Care Unit Market Development Strategy Pre and Po...
Structure-based drug design (SBDD) has become a powerful tool utilized by medicinal chemists to rationally guide the drug discovery process. Herein, we describe the use of SPROUT, a de novo-based program, to identify an indazole-based pharmacophore for the inhibition of fibroblast growth factor receptor (FGFR) kinases, which are validated targets for cancer therapy. Hit identification using SPROUT yielded 6-phenylindole as a small fragment predicted to bind to FGFR1. With the aid of docking models, several modifications to the indole were made to optimize the fragment to an indazole-containing pharmacophore, leading to a library of compounds containing 23 derivatives ...
A method of rational drug design includes simulating polypeptides in a way that predicts the most probable secondary and/or tertiary structures of a polypeptide, e.g., an oligopeptide, without any presumptions as to the conformation of the underlying primary or secondary structure. The method involves computer simulation of the polypeptide, and more particularly simulating a real-size primary structure in an aqueous environment, shrinking the size of the polypeptide isobarically and isothermally, and expanding the simulated polypeptide to its real size in selected time periods. A useful set of tools, termed Balaji plots, energy conformational maps, and probability maps, assist in identifying those portions of the predicted peptide structure that are most flexible or most rigid. The rational design of novel compounds, useful as drugs, e.g., bioactive peptidomimetic compounds, and constrained analogs thereof, is thus made possible using the simulation methods and tools of the described invention.
Final Year project Rational Drug Design Using Genetic Algorithm Case of Malaria Disease Supervision by Assoc.Prof.Im…
Find all books from Yi Zheng - Rational Drug Design. At you can find used, antique and new books, COMPARE results and immediately PURCHASE your selection at the best price. 9781627030076
One has to consistently looking at accelerating the drug discovery process for genomics, proteomics and in silico biology. Simulating the in vivo to in silico is a challenging task today. But today it is possible to achieve with the advancement in High performance computing power and with the software developed my efficient algorithms. There are a few software available for in silico drug design. One such product is MOE, Molecular Operating Environment developed by chemical computing group Canada. Which contains all the programs from sequence analysis protein modeling and structure based drug design ...
This webinar will provide insight into key genomic concepts and technologies that have shaped our contemporary understanding of the biology, treatment, and drug development opportunities in oncology.
The Department of Drug Design and Target Validation develops new molecular therapies for neurodegenerative and inflammatory diseases. The departments expertise is based on an in depth pharma-like understanding of scientific work and a long-lasting experience in the field of drug development. This profile encompasses the identification of new target proteins by analyzing putative pathologic post-translational modifications, the misfolding of proteins and the formation of pathological aggregates. Based on these new strategies the department develops and tests small molecules as well as biological agents (biologicals). This research is complemented by the design of new assays for the identification and diagnostic application of biomarkers aiming at monitoring the course of the disease and its therapy. The departments expertise also expands to the generation of pharmacologically relevant in vitro and in vivo models. Besides state-of-the-art methods for peptide synthesis and protein analytics ...
The production of large amount of compounds is the characterization of modern drug discovery. This huge libraries of compounds need to be examine in short periods of time. So, Computer aided drug design has came out as a method for developing candidate drug for treatment of many disease types. The discovery of drug and developing new drug is a very long term process and very costly, that is why CADD approach is used in pharmaceutical companies to resolve this issue to some extent. It is a computational approach to discover developed, enhances and analyze drug and biologically related active compounds. This approach is used for virtual screening, virtual library design, lead optimization and also used for quick evaluation of large compound to guide and speed up the development of new active biological compound ...
Professional bodies and Institutes CPD schemes are either structured as Input or Output based. Input based schemes list a precise number of CPD hours that individuals must achieve within a given time period. These schemes can also use different currencies such as points, merits, units or credits, where an individual must accumulate the number required. These currencies are usually based on time i.e. 1 CPD point = 1 hour of learning. Output based schemes are learner centred. They require individuals to set learning goals that align to professional competencies, or personal development objectives. These schemes also list different ways to achieve the learning goals e.g. training courses, seminars or e:learning, which enables an individual to complete their CPD through their preferred mode of learning. The majority of Input and Output based schemes actively encourage individuals to seek appropriate CPD activities independently. As a formal provider of CPD certified activities, SMI Group ...
J Med Chem 45:2695В-2707 Eakin AE, Guerra A, Focia PJ, Torres-Martinez J, Craig SP 3rd (1997) Hypoxanthine phospho- ribosyltransferase from Trypanosoma cruzi as a aim as a service to structure-based inhibitor design: crystallization and check studies with purine analogs. A 1999 future, randomized Gynecologic Oncology Organization (GOG) probationary of 374 patients with IB2 cervical can- cer randomly assigned patients to be treated with emission cure (outer smile radiantly and intracavitary cesium) and adju- vant extrafascial hysterectomy 3В-6 weeks later, with or with- revealed weekly intravenous cisplatin at a dose of 40 mg/m2 after 6 weeks during the extraneous radiation. These cells are titled descent places [url=]topamax 200 mg free shipping[/url] medications ending in pam. Septic shock is a medical pinch and children are for the most part admitted to an exhaustive care portion (catch sight of Chapter 31). Even retention T-cells are at the ...
Medicinal Chemistry is a highly interdisciplinary key science within pharmaceutical research, uniquely positioned at the interface to many other scientific areas. Working in close collaboration with biology, molecular modeling and screening technologies, medicinal chemists design and synthetize new bioactive compounds, aiming at the optimal balance of biological activity and physico-chemical properties. Several thousand new molecules need to be created, characterized and tested within a drug discovery project: each round of feedback provides information to guide the next design decision, until one or more potential clinical candidates are identified. Medicinal chemistry also provides tool compounds for biological research, systems biology, and assay development.. Tags: Chemistry ...
Electrostatic interactions between ligands and their receptors are important factors for molecular recognition. Assessing the ligand-receptor electrostatic complementarity provide valuable information for molecular design. In this hands-on workshop we will focus on using Flare™, Cressets structure-based design application to design ligands that are electrostatically complementary to the protein active site. You will learn how to visualize ligand-protein interactions; design new molecules in the context of the active site; easily dock new molecule designs to a protein active site; and assess the electrostatic complementarity between ligands and protein.
Cambridge Healthtech Institute & Bio-IT World Announce Upcoming Short Course: Identification of Druggable Sites for Protein-Protein Interaction Targets June 8, 2011 (6:00 - 9:00 p.m.) Royal Sonesta Hotel Boston, Cambridge, MA Register at On June 8, 2011, a dinner short course (6:00 - 9:00 p.m.) will take place at the conclusion of day one of CHIs Eleventh Annual Structure-Based Drug Design conference. Delegates attending CHIs Structure-Based Drug Design conference are invited to attend, as well as others from the local area. About the course: Despite the growing number of examples of small molecule inhibitors that disrupt protein-protein interactions (PPIs), the origin of druggability is poorly understood. This course is designed to demonstrate the use of computational methods to determine the most likely structure of the complex formed by interacting proteins, identify potentially druggable sites in the interface, determine whether the target is ...
The cloning of the genome presents huge opportunities for the pharmaceutical industry to discover new targets for the therapeutics of the future. This bodes well for future drug pipelines in the industry but raises the problem of identifying the best targets to develop out of the large number being identified. The issue of assigning some therapeutic value to newly discovered genes is also becoming increasingly important to ensure that patents for genes can be obtained. This conference will explore the latest issues in the field from technological advances to new applications of more traditional methods of target validation. Validation strategies employed by some of the biggest companies in the world will be discussed with a focus on the overall approaches rather than the technology itself. It is a must for those involved in drug research and discovery if you want to stay abreast of developments in the field. Innovations in Target Validation is organised and produced by SMi: we specialise in ...
The antiviral therapeutic area continues to rapidly generate meaningful new chemical entities; for example, for HIV alone more than 25 drugs have been approved, and in the next few years many individual drugs and single tablet regimens will be approved for the treatment of hepatitis C virus infection. The increasing success in the antiviral area could be due to targeting drugs at non-self genomes and to the patient population that is tolerant of manageable side effects and adaptable to inconvenient dosing.Aimed at medicinal chemists and emerging drug discovery scientists, the book is organized according to the various strategies deployed for the discovery and optimization of initial lead compounds. This book focuses on capturing tactical aspects of problem solving in antiviral drug design, an approach that holds special appeal for those engaged in antiviral drug development, but also appeals to the broader medicinal chemistry community based on its focus on tactical aspects of drug design.
Suggestions for paper or patent submissions.. We have cooperated with many research institutions and biotechnology companies and accumulated extensive experience in drug design. Says Gary Williams, Senior Scientist of ComputaBio, Our efficient and responsive team of drug design professionals would become your best partners in drug discovery.. To better support scientists in drug discovery and development, ComputaBio also provides molecular dynamics simulations, biological data analysis, protein sequence analysis, protein structure modeling, virtual screening, and other computational biology solutions. Visit the companys website for more details of its services and the company itself. Inquiry could be sent either via email ([email protected]) or on the specific service website.. About ComputaBio. Over the past decade, ComputaBio has been continuously providing professional computational biology services to research institutions and biotech companies worldwide. The company is ...
Clinipace can navigate challenges in the development of treatments for infectious diseases, and create opportunities in the evaluation of new agents.
Drug Design and Discovery Research Papers - access all research publised in Drug Design and Discovery on worlds leading knowledge platform Knimbus
Letters in Drug Design & Discovery is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery....
Letters in Drug Design & Discovery is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery....
Letters in Drug Design & Discovery is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.
A primary objective of our research is to design new antibacterial agents based on novel mechanisms of action. Currently, all clinically used antibiotics act by one of a limited number of mechanisms (e.g. inhibition of protein synthesis, DNA synthesis, cell-wall synthesis, and RNA transcription). We utilize available data from experimental genetic approaches to identify candidate bacterial targets. In cases where the structure and enzymology of the bacterial enzyme is known, we rationally design substrate mimics or transition-state inhibitors. However, for many potential targets there is inadequate structural information available to permit such a structure-based drug design approach. In these cases we develop high-throughput-screening (HTS) assays that allow us to identify a lead candidate molecule. Once a small molecule inhibitor is identified against the targeted enzyme we then apply medicinal chemistry efforts to methodically optimize the inhibitor scaffold. Structure- and/or ligand-based ...
2G0G: Structure-Based Drug Design of a Novel Family of PPARgamma Partial Agonists: Virtual Screening, X-ray Crystallography, and in Vitro/in Vivo Biological Activities
Computer-Assisted Molecular Design (CAMD)- An Overview By Horst Friihbeis, Robert Klein, and Holger Wallmeier Dedicated to Professor Heinz Harnisch on the occasion ofhis 60th birthday A new instrument, long established as C A D in engineering, is beginning to make its presence felt in chemical research laboratories: Computer-Assisted Molecular Design (CAMD). The combined use of computer graphics and theoretical chemistry is opening u p new perspectives in molecular research. Structures and properties of molecules such as spacefilling, charge distribution, or dynamic behavior can be determined and used for comparison. For research on complex systems like biomolecules (protein engineering), this new approach turns out to be indispensable. 1. Introduction Computer-assisted molecular design is a new approach to molecular research using methods from theoretical chemistry. The essential feature is the use of models and their realization on a computer. This may be regarded as the continuation of an ...
|i|Journal of Drug Design and Medicinal Chemistry (JDDMC)|/i| is a peer-reviewed scientific journal devoted to the development of innovative science, technology and medicine with a focus on the multidisciplinary fields of drug designing. It is the aim of JDDMC to capture significant research related to drug designing/modeling that highlights new concepts, insight and new findings within the scope of drug designing chemistry.
Pharmacokinetic information from FDA and EMA regulatory documents informs translational and clinical development decisions and may lead to more successful drug development and regulatory approval strategies. Pharmacokinetic information from FDA and EMA re...
In this Letter, we provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. During the course of our structure-based drug design efforts, we discovered two distinct binding modes within the COX-2 active site for differently substituted members of this class. The challenge of a undesirably long human half-life for the first clinical candidate 1t(1/2)=360h was addressed by multiple strategies, leading to the discovery of 29b-(S) (SC-75416) with t(1/2)=34h. The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life.,Wang JL, Limburg D, Graneto MJ, Springer J, Hamper JR, Liao S, Pawlitz JL, Kurumbail RG, Maziasz T, Talley JJ, Kiefer JR, Carter J Bioorg Med Chem Lett. 2010 Jul 24. PMID:20709553[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine ...
Frontiers in Drug Design and Discovery Volume 7 by Atta-ur-Rahman, Mohammad Iqbal Choudhary Frontiers in Drug Design and Discovery is an eBook series devoted to publishing the latest and the most important advances in drug design and discovery. Eminent scientists have contributed chapters focused on all areas of rational drug design and…
Virtual screening of chemical databases to targets of known three-dimensional structure is developing into an increasingly reliable method for finding new lead candidates in drug development. Both better scoring functions and novel docking strategies contribute to this trend, although no completely satisfying approach has been established yet. This is not surprising since the approximations which are needed to achieve a reasonable screening rates impose significant restrictions on the virtual representation of the physical system. Relaxation of these restrictions, such as permitting ligand or receptor flexibility, potentially increase the reliability of the scoring process, but come at a high computational cost. While ligand flexibility is now routinely considered in many atomistic in-silico screening methods, accounting for receptor flexibility still poses significant challenges. Using the thymidine kinase inhibitors as a prototypical example we document the shortcoming of rigid receptor screens in a
C-H functionalization is a powerful addition to the toolbox of the medicinal chemist. Modern C-H functionalization techniques hold the potential to enable the rapid exploration of structure activity relationships (SAR), the generation of oxidized metaboli...
In this seminar, we review the importance of chromatographic selectivity from a theoretical and practical perspective and how this relates to analyte resolution for method development. With an understanding of selectivity and using a variety of chromatographic data, we discuss phase design principles and how it is possible to introduce functionality that enhances selectivity, whilst maximising other desirable phase attributes such as phase stability, reproducibility and mechanisms of interaction. The resulting novel phases are explored for their improved chromatographic performance, selectivity and value in method development for a range of analytes and separations. Finally, method development approaches are discussed and pragmatic, simple method development platforms are illustrated based upon rational phase and eluent choice ...
Hepatic intrinsic clearance (CLint) is an important parameter for a drug candidate as it influences oral bioavailability as well as systemic exposure. Thus, it is common to determine this property early in drug discovery so that it can act as a compound selection criterion as well as aid medicinal chemists in drug design. The translation of drug leads into clinical candidates could be improved by the further development of in silico tools for reliable prediction of human clearance. The major enzymatic system responsible for metabolism of xenobiotics is the cytochrome P450 (P450) family (Nebert and Russell, 2002). P450s are responsible for more than 75% of drug metabolism, and the major isoform among these enzymes is CYP3A4, which is responsible for the metabolism of ∼50% of known xenobiotics in humans. Other important isoforms include CYP2C9, CYP2D6 and CYP1A2 (Guengerich, 1999, 2008). A joint team comprising of members from the International Consortium for Innovation and Quality in ...
A HIV-1 tier program continues to be developed to categorize the many subtype infections predicated on their level of sensitivity to vaccine-induced neutralizing antibodies (NAbs): tier 1 with finest level of sensitivity, tier 2 becoming delicate moderately, and tier 3 becoming the least delicate to NAbs (Mascola et al. short-duration (37C41 several BIBW2992 weeks) research. In long-duration (76C80 several weeks) research, the industrial vaccine afforded a mixed safety price of at least 46% contrary to the tier-2 and tier-3 infections. Notably, safety rates observed listed below are far better than recently reported HIV-1 vaccine trials (Sanou et al., The Open AIDS 2012; 6:246-60). Prototype vaccine protection against two tier-3 and one tier-2 viruses was more effective than commercial vaccine. Such protection did not correlate with the presence of vaccine-induced NAbs to challenge viruses. This is the first large-scale (228 laboratory cats) study characterizing short- and long-duration ...
Current Computer-Aided Drug Design aims to publish all the latest developments in drug design based on computational techniques. The field of computer-aided drug design has had extensive impact in the area of drug design. Current Computer-Aided Drug Design is an essential journal for all medicinal chemists who wish to be kept informed and up-to-date with all the latest and important developments in computer-aided methodologies and their applications in drug discovery. Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of computational techniques for drug design, screening, ADME studies, etc., providing excellent rationales for drug development ...
Role of Molecular Docking in Computer-Aided Drug Design and Development: 10.4018/978-1-5225-0362-0.ch001: Molecular Docking is widely used in CADD (Computer-Aided Drug Designing), SBDD (Structure-Based Drug Designing) and LBDD (Ligand-Based Drug Designing). It is
Ted L. Field, Computer-Aided Drug Design Using Patented Compounds: Infringement in Cyberspace?, 34 J. Marshall L. Rev. 1001 (2001). ...
This workshop aims to present several computer-aided drug design tools developed at SIB. Several examples are taken from different therapeutical fields. The exercises are available to a wide audience. ...
GAO discussed the National Aeronautics and Space Administrations (NASA) strategy for developing the Earth Observing System Data and Information System (EOSDIS). GAO noted that: (1) NASA is developing EOSDIS to perform extensive data processing, archiving, and distribution functions to serve the needs of scientists performing integrated, interdisciplinary studies of Earth; (2) the intended scope of EOSDIS far exceeds that of any previous civilian data management system; (3) the NASA EOSDIS development strategy does not adequately identify and mitigate the significant technological risks inherent to a project of this size, scope, and technical complexity; (4) the NASA near-term EOSDIS prototype projects do not address critical areas where technical feasibility is in question and are not substantial enough to allow users to assess key EOSDIS functions; and (5) NASA did not specifically address certain key technologies in its development strategy, including new data-base search techniques and data ...
The aim of the 6th RSC-BMCS Fragment-based Drug Discovery meeting will be to continue the focus on case studies in Fragment-based Drug Discovery that have delivered compounds to late stage medicinal chemistry, preclinical or clinical programmes. The Fragment series was started in 2007 and continues with the theme, having over three-quarters of the presentations focused on case studies. The conference will include successful examples from all types of fragment-based approaches, including high concentration, NMR, SPR and X-ray screening ...
Clinical Drug Development MRes at University College London, listed on - a comprehensive database of Masters, MSc, MA, MPhil & MRes courses in the UK & Ireland
As a joint meeting, the 26th Medicinal Chemistry Conference of GP2A and 32nd Journées Franco-Belges de Pharmacochimie took place between 13th and 15th June at Asnelles sur Mer (Normandie, France), providing a unique opportunity for a wide group of European medicinal chemists to engage. Topics included chemical tools for medicinal chemistry, protein-protein interactions, epigenetics, natural product-inspired molecules, computer-aided drug design, and new strategies for the design and development of drugs. Abstracts of invited lectures, proffered young researcher communications, flash communications and posters presented during the meeting are collected in this report.
The goal of this course is to expose the participants to 3-dimensional structures of proteins. It describes the experimental methods used to solve these structures, and databases used to archive, annotate and classify protein structures. Analysis and visualisation software will be used to display, analyze, compare and interpret protein structures. Students will also be introduced to protein structure prediction by homology modeling techniques.. The second part of the course is dedicated molecular modelling, introduction to docking of small molecules (drugs, peptides) to large macromolecules and Molecular graphics. ...
Frontiers in Cardiovascular Drug Discovery is an eBook series devoted to publishing the latest and the most important advances in Cardiovascular drug design and discovery. Eminent scientists write contributions on all areas of rational drug design and drug discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, recent important patents, and structure-activity relationships. The eBook series should prove to be of interest to all pharmaceutical scientists involved in research in cardiovascular drug design and discovery. Each volume is devoted to the major advances in cardiovascular drug design and discovery. The eBook series is essential reading to all scientists involved in drug design and discovery who wish to keep abreast of rapid and important developments in the field ...
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With bioinformatics, the drug development process has become much more efficient, with more rapid design and development, along with less overall cost and risk. (b) RasMol. University. Development of efficient algorithms to … Structural Bioinformatics 2004 Prof. Haim J. Wolfson 2 Objectives of the course Understanding protein function. The computational … It is anticipated to grow at a CAGR of 14.0% from 2019 to 2030. A Deep Insight to Ligand-based Computer-Aided Drug Design. Yang SY. Drug Designing 1. In pharmaceutical, medicinal as well as in other … Whittaker,2003). The applications are: 1. Uploaded by. Course. Applications of Bioinformatics in Drug Discovery. Bioinformatics: Benefits to Mankind Himanshu Singh* Dept. As stated earlier, from the pharmaceutical industry point of view, Bioinformatics is the key to rational drug design. 41. … ‎Drug … Bioinformatics … Pharmacophore modeling and applications in drug discovery: challenges and recent advances. Computer Applications in ...
The Mycobacterium tuberculosis extracellular zinc metalloprotease 1 (Zmp1) has been proposed to play a key role in phagosome maturation and to enhance the survival of Mycobacterium tuberculosis in the host. Consequently, small molecule inhibitors of Zmp1 are of pivotal importance as a tool to better understand the pathogenicity of Zmp1 and as lead candidates for pharmacological intervention. Here we combined in silico structure-based inhibitor design with biochemical studies to discover and characterize the first potent competitive Zmp1 inhibitor showing a Ki of 94 nM and a high selectivity for Zmp1 with respect to human Neprilysin.. ...
Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.. ...
The reason for the low number of successful new CNS drugs is the subject of debate, although it is undoubtedly related to their higher attrition rate during development, particularly from issues related to failures of on-target biological hypotheses. To address this problem, there has been a recent emphasis on research to tackle these issues at an earlier stage in the drug discovery pathway. In particular, there has been increased interest in target discovery both for the identification of novel targets and reducing the subsequent failure from incorrect biological hypotheses through early validation.. Target discovery, which involves the identification and early validation of disease-modifying targets, is an essential first step in the drug discovery process. Furthermore, although the knowledge of the target for a small molecule drug is not required by the FDA for drug development, it is crucial information if the drug discovery process is to be made more efficient and effective. Identifying the ...
With the rapid development in the amount of molecular biological structures, computational molecular docking (CMD) approaches become one of the crucial tools in rational drug design (RDD). Currently, number of researchers are working in this filed to overcome the recent issues of docking by using genetic algorithm approach. Moreover, Genetic Algorithm facilities the researchers and scientists in molecular docking experiments. Since conducting the experiment in the laboratory considered as time consuming and costly, the scientists determined to use the computational techniques to simulate their experiments. In this paper, auto dock 4.2, well known docking simulation has been used to perform the experiment in specific disease called malaria. The genetic algorithm (GA) approach in the autodock4.2 has been used to search for the potential candidate drug in the twenty drugs. It shows the great impacts in the results obtained from the CMD simulation. In the experiment, we used falcipain-2 as our ...
Welcome to the Official Web Site of ESIS Rational Drug Design & Development Group at Faculty of Pharmacy, Ankara University, TURKEY.|br /> Heads of ESIS Research Group: Prof. Esin AKI (SENER) - Prof. Ismail YALCIN
GENERAL INFORMATION: AMS-535 provides an introduction to the field of computational structure-based drug design. The course aims to foster collaborative learning and will consist of presentations by myself, course participants, and guest lecturers arranged in five major sections outlined below. Presentations should aim to summarize key papers, theory, and application of computational methods relevant to computational drug design. Grades will be based on the quality of the talks, participation in class discussion, attendance, quizzes, and a final. ...
Chris is a leader in pharmaceutical research with expertise in fragment-based drug discovery, structure-based drug design, target analysis, kinases, phosphodiesterases, nuclear hormone receptors, and proteases. In his current role, as Associate Director of Structural Biology at Astra Zeneca, he is leading a team of scientists supporting pipeline projects with structural insights.. In his previous role as a senior principal scientist at Pfizer for over 13 years, he developed the core capabilities in macromolecular crystallography with emphasis on the application of structural information in the drug discovery process. Chris acquired a D. Phil in macromolecular crystallography and was also a postdoctoral research associate at the University of Oxford.. Chris has been an enthusiastic contributor and strong supporter of the Cambridge Pharmaceutical Consortium. The consortium has brought together pharmaceutical companies, the University of Cambridge, the Medical Research Councils Laboratory of ...
The 5 Day eCheminfo Hands-on Drug Discovery Workshop Week will take place this year 21-25 July 2008 at the Medical Sciences Teaching Center, Oxford University, Oxford, UK. Topics to be covered include Virtual Screening & Docking; Structure-based Drug Design; Ligand Optimisation & Library Design; Structure Search, Similarity and Property Estimation; Data Mining, Analysis & Visualisation; Pharmacophore Modelling for Lead Identification; Fragment-based Drug Design; QSAR-based Predictive Toxicology; and Quantitative Spectrometric Data-Activity Relationship Modelling. These workshops are aimed to provide a set of stimulating workshops using latest advanced modelling techniques of relevance to chemists, life scientists and modellers working in drug discovery. The workshop group studies problems with hands-on examples using leading-edge software and discusses complex issues highlighted by examples and case studies presented by instructors. A variety of leading drug discovery software packages and an IT ...
The landscape of oncology therapeutics has shifted in the last decade from cytotoxic compounds to molecularly targeted agents that aim to deliver improved efficacy in molecularly defined susceptible cancers. The use of companion diagnostics in oncology is making the promise of patient stratification and the delivery of precision medicine more of a reality. In 2011 alone, the FDA approved 3 oncology agents indicated for biomarker-identified patient subpopulations: brentuximab vedotin (Adcetris; Seattle Genetics) for CD30-expressing Hodgkin lymphoma, crizotinib (Xalkori; Pfizer) for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer, and vemurafenib (Zelboraf; Genentech) for metastatic melanoma with the BRAF (serine/threonine-protein kinase B-raf) V600E mutation (10).. Clinical trials for molecularly targeted therapies are more likely to prove effective when a strong biological hypothesis is evaluated in patients selected on the basis of the presence of a specific ...
ESMO is a Swiss-registered not-for-profit organisation. All funding for this site is provided directly by ESMO or via grants from the sponsors and supporters.. Via L. Taddei 4, 6962 Viganello - Lugano - CH © Copyright 2017 European Society for Medical Oncology All rights reserved worldwide.. ...
Saturated azaheterocycles are popular in modern drug discovery programs. More than 50 FDA-approved drugs containing a fragment of pyrrolidine and piperidine have appeared on the market. Pyrrolidine/piperidine-based azasugars and their analogues are potent glycosidase inhibitors. These unique molecules promise a new generation of iminosugar-based medicines for a wide range of diseases. For example, a bioactive azasugar includes the anti-diabetic drug Glyset. In this context, herein we have designed and synthesized a library of sugar-like derivatives for drug design.. ...
Clumps of proteins that accumulate in brain cells are a hallmark of neurological diseases such as dementia, Parkinsons disease and Alzheimers disease. Over the past several years, there has been much controversy over the structure of one of those proteins, known as alpha synuclein.. MIT computational scientists have now modeled the structure of that protein, most commonly associated with Parkinsons, and found that it can take on either of two proposed states - floppy or rigid. The findings suggest that forcing the protein to switch to the rigid structure, which does not aggregate, could offer a new way to treat Parkinsons, says Collin Stultz, an associate professor of electrical engineering and computer science at MIT.. If alpha synuclein can really adopt this ordered structure that does not aggregate, you could imagine a drug-design strategy that stabilizes these ordered structures to prevent them from aggregating, says Stultz, who is the senior author of a paper describing the findings ...
Preface ix 1 Introduction 1. 1.1 New Drugs and Medical Progress 1. 1.2 The Challenge of New Drug Discovery 5. References 7. 2 Mechanism of Drug Action: Basic Concepts 9. 2.1 Pharmacodynamic Phase: Drug-Receptor Interactions 10. 2.1.1 The Receptor Concept and Receptor Types 10. 2.1.2 Ligand-Receptor Binding 12. 2.1.3 Receptor Occupancy and Activation 16. 2.2 Pharmacokinetic Phase: ADME 20. 2.2.1 Drug Absorption and Distribution 20. 2.2.2 Drug Metabolism and Excretion 22. 2.2.3 Basic Pharmacokinetic Concepts 26. 2.3 Structural Requirements: Keeping It Drug-Like 29. 2.3.1 The Drug-Like Chemical Space 29. 2.3.2 Oral Drugs: The Challenge of Bioavailability 31. References 33. 3 The Drug Discovery and Development Process 39. 3.1 Discovery Research 39. 3.1.1 Prediscovery 39. 3.1.2 Target Identification 41. 3.1.3 Target Validation 42. 3.1.4 Target-to-Hit and Hit-to-Lead Development 42. 3.1.5 Early Distribution and Safety Tests 46. 3.1.6 Lead Optimization 48. 3.2 Preclinical Development 49. 3.2.1 ...
Both docking cavities identified by the floodfill algorithm are in close vicinity to and in close contact with the earlier suggested NP epitope sequences studied in a previous study [21] (see Figure 1). Site 2 occupies an arginine-rich region of the RNA-binding groove and forms extensive contacts with another NP-conserved epitope sequence R174-K184, which makes the site very attractive for targeting NP. Meanwhile, Site 1 has only minor contact with another epitope sequence, I265-S274. Surprisingly, both Site 1 and Site 2 are distant from the proposed binding site of the recent NP inhibitor nucleozin, which is marked by the residue Y289 [17] on Figure 1.. The demonstrated level of animal protection in treatments with F66 reached 40%, which is comparable to the protection provided by treatment with rimantadine in a similar experiment (60%). In the emergency prophylaxis study, the compound application increased the lifetime of the mice by 2.7 days. The results are inferior to the protection level ...
International Conferences and meetings provide valuable opportunities for global assembling of Speakers, Researchers, Experts and Industrialists at Top Chemistry and Drug Design Conferences, Rome, Chemistry Conferences and Chemistry Conferences held during May 20-21, 2019 Rome, Italy to establish and build up the Chemistry and Drug Design community.
Over the past decades, molecular docking has become an important element for drug design and discovery. Many novel computational drug design methods were
One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. discovery are urgently required if we are to tackle the multiple global health challenges of emerging and neglected infectious diseases for which there is relatively little basic science investment. Recently, Simmons and and [17]. This pathway is present in bacteria, fungi, plants and apicomplexan parasites, but not in mammals, and hence represents an ideal target for the development of antibacterial agents, as these agents would be expected to have a spectrum of antibacterial activity restricted to those human pathogens expressing DHQase such as and DHQase was used as a starting point to identify novel inhibitors [18]. While approximately 100 molecules with more than 50 per cent inhibition of DHQase enzyme activity at a concentration of 20 g ml?1 were identified in the primary screening, only one confirmed inhibitor against DHQase was ...
Cheminf is the place to share my research interests and free computer-aided drug design (CADD) software developed during my research activity. The Clusterizer/DockAccessor software and tutorial are freely available here.. NEW! Clusterizer/DockAccessor 1.1 available ...
Supplementary Materialsmicroorganisms-08-00703-s001. from being fully exploited. Specifically, their antiviral activity hasnt been investigated. In todays study, a -panel of SL analogs continues to be evaluated for antiviral activity against HCMV. We demonstrate that TH-EGO and EDOT-EGO inhibit HCMV replication in vitro considerably, impairing past due protein expression. Furthermore, we show which the SL-dependent induction of apoptosis in HCMV-infected cells is normally a contributing system to SL antiviral properties. General, our outcomes indicate that SLs could be a appealing alternative to nucleoside analogs for the treatment of HCMV infections. subfamily, is one of the most significant opportunistic human pathogens. Although HCMV rarely causes symptomatic clinical manifestations in immunocompetent individuals, it induces severe morbidity and mortality in the immunocompromised population, following either primary infection or reactivation, leading to gastro-intestinal diseases, ...
In contrast to traditional methods of drug discovery (known as forward pharmacology), which rely on trial-and-error testing of chemical substances on cultured cells or animals, and matching the apparent effects to treatments, rational drug design (also called reverse pharmacology) begins with a hypothesis that modulation of a specific biological target may have therapeutic value. In order for a biomolecule to be selected as a drug target, two essential pieces of information are required. The first is evidence that modulation of the target will be disease modifying. This knowledge may come from, for example, disease linkage studies that show an association between mutations in the biological target and certain disease states.[16] The second is that the target is druggable. This means that it is capable of binding to a small molecule and that its activity can be modulated by the small molecule.[17] Once a suitable target has been identified, the target is normally cloned and produced and ...
The successful applicant have or will have a PhD degree in a subject relevant to our research, including Computational Biology (bioinformatics, systems biology), Computer Science, Statistics, Pharmacology, Chemistry (computational chemistry, medicinal chemistry) and Biology (structural biology, molecular and cell biology). At least one of the following conditions must be satisfied: 1) a strong background in software engineering and the ability to develop novel biofinformatic software/databases, 2) experience in handling large-scale biological data such as those from transcriptomic and proteomic experiments and 3) the ability to analyze small-molecule compounds and their targets using tools in chemoinformatics and computer-aided drug design.. A good balance of scientific and interpersonal skills will be essential and willingness to tackle interdisciplinary research questions is advantageous.. [Location] ...
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Read News from IOTA Pharmaceuticals based in UK, a leading service provider for Fragment based Drug Discovery based molecular design, compound screening, lead discovery
INTRODUCTION. Structure-based drug design seeks to identify and optimize specific attractive interactions between two partner molecules in biological systems between ligands and their host molecules, typically proteins. The simple answer to whats holding the industry back in terms of adoption of latest drug discovery techniques is Education. There simply arent enough individuals trained on the use of Proteomics, Virtual Screening, Molecular Docking, Simulations, Dynamics and ADMET- multidisciplinary approaches, which is why we continue to offer courses, for both novice and experienced users, on the use of this technology as it applies to their research functions.. This 1 day training course will focus on the use of efficient technologies used in the discovery & designing of Drugs on the basis of the biological targets critical to the disease condition.. During this course, you will be introduced to basic principles of Rational Drug Design along with Proteomics in Drug Discovery. The course ...
Start Term: Fall. The work of developing new drugs to treat diseases begins with the medicinal chemist. In this program, youll build on your masters degree in medicinal chemistry with advanced knowledge of the behavior of chemical substances at the molecular level. During this doctoral program, youll have the opportunity to work alongside professional experts in modern laboratories to design, synthesize, and analytically examine drug compounds. Youll study how chemical substances behave at a molecular level, and how the chemical properties affect drug kinetics, absorption, distribution, metabolism, and excretion. And youll participate in research directed toward a fuller understanding of pharmacological actions, leading to improved drug design.. Students may elect to complete a minor concentration in drug metabolism, integrating the knowledge of drug metabolism, analysis of pharmaceuticals in biological fluids and incubation mixtures, enzyme kinetics, and animal care and use.. ...
Tuesday, June 11, 2013 Pharmacy Building, KU West Campus Presentations: Room 2020 Poster Session: School of Pharmacy Atrium 8:00 a.m.- 4:30 p.m.
Recently, metabolite characterization has shifted from the development stage of the drug discovery process and has become an integral component of early discovery-stage research. Concomitant with this shift has been a change in the type of information sought from metabolic studies. Although detailed qualitative and quantitative analysis of the metabolic pathway of a lead candidate continues to be an essential element of the drug development process, biotransformation information gleaned at the discovery stage can be used to guide synthetic chemistry efforts to either block or enhance metabolism with a view to optimizing the pharmacokinetic and safety profiles of newly synthesized compounds. Additionally, data on the metabolic fate of a large number of compounds may facilitate the development of structure-activity relationships for metabolism.. The availability of tandem mass spectrometers (McLafferty, 1980; Busch et al., 1988) has given the drug metabolism scientist a very powerful tool for ...
Advertisement. It was later discovered that the fatigued soldier suffered from good ol fashioned flu and was overcome by pneumonia - complicated by the stress and workload that come with being in the military. The U.S government prevented patients from taking action against negligent pharmaceutical companies by offering indemnity to the manufacturers. Todays swine flu threat is being promoted with the same fuzzy generalizations that spurred the demand for vaccines in 1976. The virus is still around and ready to explode, warned William Schaffner, an influenza expert (or pharmaceutical lapdog depending on how you look at it) at the Vanderbilt University School of Medicine. Were potentially looking at a very big mess, he insists. Yet, he provides no laboratory evidence whatsoever to back up his alarmist claims. In fact, as highlighted on the nationally syndicated Robert Scott Bell radio show (Google it), the World Health Organization (WHO) has issued a directive to stop testing for the ...
Although anti-retroviral therapy (ART) is impressive in suppressing HIV replication, it fails to eradicate the virus from HIV-infected individuals. reactivated following the interruption of anti-retroviral therapy (ART). Despite an early initiation of ART, viral reservoirs are established and persist as exhibited in the case of the Mississippi baby and from recent studies of the SIV model of AIDS. Therefore, new strategies are needed for the eradication of the latent HIV reservoirs. We found that ingenol-3-angelate (PEP005), a member of the new class of anti-cancer ingenol compounds, effectively reactivated HIV from latency in primary CD4+ T cells from HIV infected individuals receiving ART. Importantly, a combination of PEP005 and JQ1, a p-TEFb agonist, reactivated HIV from at level on average 7 latency.5-fold higher in comparison to PEP005 alone. The strength of synergistic ramifications of PEP005 and JQ1 offer novel possibilities for evolving HIV eradication strategies in the foreseeable ...
Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9780120603084. Ojasoo T, Delettré J, Mornon JP, Turpin- ... Unlisted Drugs. Pharmaceutical Section, Special Libraries Association. 1982. Batynid. C. Each dragee contains: normethandrone, ... 898-. ISBN 978-1-4757-2085-3. "Methylestradiol". Retrieved 2 January 2016. IARC Working Group on the Evaluation of ... J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp ...
90-. ISBN 978-1-84184-757-3. Daniel Lednicer (4 March 2009). Strategies for Organic Drug Synthesis and Design. John Wiley & ... Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9781483216102. Raynaud, J. P. (1971). Metabolism of ... Norgestrienone is the generic name of the drug and its INN. It is also known by its developmental code names RU-2010 and A-301 ... Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. ...
... drug design; nanoparticle structure and energetics; and density functional theory, including the Minnesota Functionals. He has ...
Raynaud, J.P.; Ojasoo, T.; Bouton, M.M.; Philibert, D. (1979). Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X ... Side Effects of Drugs Annual. 25. pp. 478-502. doi:10.1016/S0378-6080(02)80047-2. ISBN 9780444506740. ISSN 0378-6080. Leinung ... ISBN 978-3-642-60107-1. Stege R, Carlström K, Collste L, Eriksson A, Henriksson P, Pousette A (1988). "Single drug ... ISBN 978-0-12-137250-7. Stege R, Carlström K, Collste L, Eriksson A, Henriksson P, Pousette A (1988). "Single drug ...
PMID 14793878.CS1 maint: untitled periodical (link) Martin-Smith M (1971), In: Ariens EJ (ed.), "Drug Design". Vol. 2. Academic ... Drugs. 4 (3-4): 163-226. doi:10.2165/00003495-197204030-00002. PMID 4264763. S2CID 20303531. Thompson MA (1980). Br. J. Hosp. ...
Drug design; Biology of peptides, nucleoside derivatives and modified oligonucleotides Biopolym. Cell is issued bimonthly, with ...
Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9780120603084. v t e. ... It is a potent antagonist of the mineralocorticoid receptor and is more potent than the related drug SC-5233 (of which SC-8109 ...
Raynaud, J.P.; Ojasoo, T.; Bouton, M.M.; Philibert, D. (1979). Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X ... Gestrinone is the generic name of the drug and its INN, USAN, BAN, and JAN. It is also known by its developmental code names A- ... THG was banned by the Food and Drug Administration (FDA) in 2003. Gestrinone was introduced for medical use in 1986. ... 57-. ISBN 978-1-316-21414-5. "Helping athletes compete drug-free" (PDF). Canadian Centre for Ethics in Sport. May 2000. p. 34. ...
Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9780120603084. García-Becerra R, Ordaz-Rosado D, Noé G, ...
... drug design; and technology, equipment and product design for the oil and gas and chemical industries. These fields were chosen ... This is designed to ensure that there is a demand for the research being undertaken and that the results will lead to products ... Each of these sectors tends to involve large companies equipped with design bureaux and laboratories. There are, however, also ...
Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9781483216102. Ojasoo T, Raynaud JP (November 1978). " ... Moxestrol is the generic name of the drug and its INN. It is also known by its developmental code name R-2858 or RU-2858. ... 184-. ISBN 978-1-4613-9208-8. J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and ...
Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9780120603084. Attardi BJ, Hild SA, Reel JR (June 2006 ... It is also commonly known as 7α-methyl-19-nortestosterone (MENT). J. Elks (14 November 2014). The Dictionary of Drugs: Chemical ... Expert Opin Emerg Drugs. 17 (2): 239-59. doi:10.1517/14728214.2012.683411. PMID 22612692. S2CID 22068249. Anderson RA, Wallace ... Trestolone is the generic name of the drug and its INN. ... Nieschlag E, Kumar N, ...
Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9780120603084. Kohtz, Amy S.; Frye, Cheryl A. (2012). " ... The drug was under investigation by Roussel Uclaf for potential medical use, but was abandoned in favor of nonsteroidal ... The drug is a derivative of the extremely potent androgen/anabolic steroid metribolone (R-1881; 17α-methyltrenbolone), and has ... 1-. ISBN 978-3-642-80859-3. Raynaud JP, Ojasoo T (November 1986). "The design and use of sex-steroid antagonists". J. Steroid ...
Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9780120603084. Ojasoo T, Raynaud JP (November 1978). " ... The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 899-. ISBN 978-1-4757-2085- ...
"Protein-Ligand Docking in Drug Design: Performance Assessment and Binding-Pose Selection". Rational Drug Design. Methods in ... Docking is most commonly used in the field of drug design - most drugs are small organic molecules, and docking may be applied ... "Understanding the challenges of protein flexibility in drug design" (PDF). Expert Opinion on Drug Discovery. 10 (12): 1301-13. ... Molecular docking is one of the most frequently used methods in structure-based drug design, due to its ability to predict the ...
... benefit-design consultation; drug-utilization review; formulary management; and medical and drug data analysis services to ... Thomas, Katie (2013-03-18). "U.S. Drug Costs Dropped in 2012, but Rises Loom". The New York Times. Retrieved 2013-11-20. "Drug ... the Express Scripts Drug Trend Report provides detailed analysis of prescription drug costs and utilization. Now a web-based ... Glaser Drug Company sold its Express Scripts partnership interest back to Sanus before it was acquired by chain SupeRx in 1989 ...
Rational drug design. Boca Raton: CRC Press. ISBN 0-8493-7818-4.CS1 maint: extra text: authors list (link) Ganten, edited by ... Zwieten, edited by Pieter A. van; Greenlee, William J. (1997). Antihypertensive drugs. Amsterdam, the Netherlands: Harwood ...
Carr, R. A.; Congreve, M; Murray, C. W.; Rees, D. C. (2005). "Fragment-based lead discovery: Leads by design". Drug Discovery ... Its proprietary drug discovery platform, Pyramid™, can effectively identify novel small molecule drugs for key disease targets ... "Structural biology and drug discovery". Drug Discovery Today. 10 (13): 895-907. doi:10.1016/S1359-6446(05)03484-7. PMID ... Several compounds from drug discovery collaborations with Astex have been advanced by Astex's biopharma partners into clinical ...
Carbohydrates in Drug Design. pp. 277-308. ISBN 0-8247-9982-8. {{U.S. Pharmacopeia Heparin Stage Two Monograph Revisions Open ...
He is known for his research in the fields of structural biology and drug designing. His studies have been documented by way of ... "Workshop on Advances in Computer Aided Drug Design" (PDF). vLife. August 2010. Retrieved 24 January 2018. "Past Conferences". ... Drug Design. 79 (1): 143-147. doi:10.1111/j.1747-0285.2011.01258.x. ISSN 1747-0285. PMID 21995306. Kumarevel, Thirumananseri; ... others and has delivered invited speeches at many seminars which include the Workshop on Advances in Computer Aided Drug Design ...
Drug Design. 81 (5): 557-576. doi:10.1111/cbdd.12125. ISSN 1747-0277. PMID 23452185. Wim Dehaen; Vasiliy A. Bakulev; Edward C. ...
November 1998). "Rational drug design and synthesis of a highly selective nonpeptide delta-opioid agonist, (4aS*,12aR*)-4a-(3- ... Drug Design and Discovery. 17 (4): 325-30. PMID 11765135. Nagase H, Kawai K, Hayakawa J, Wakita H, Mizusuna A, Matsuura H, et ... TAN-67 (SB-205,607) is an opioid drug used in scientific research that acts as a potent and selective δ-opioid agonist, ...
"Design of potent IGF1-R inhibitors related to bis-azaindoles". Chemical Biology & Drug Design. 76 (2): 100-6. doi:10.1111/j. ... "Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode". ... "Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pK a Polar Moiety". ACS ... "Structure-Guided Design of Group I Selective p21-Activated Kinase Inhibitors". Journal of Medicinal Chemistry. 58 (12): 5121-36 ...
Drug Design. 85 (2): 99-106. doi:10.1111/cbdd.12381. PMC 4456024. PMID 24954187. Wang X, Li MX, Sykes BD (Aug 2002). "Structure ... Drug Discovery. 14 (5): 313-28. doi:10.1038/nrd4554. PMID 25881969. S2CID 21888079. Hwang PM, Cai F, Pineda-Sanabria SE, Corson ... Lindert S, Li MX, Sykes BD, McCammon JA (Feb 2015). "Computer-aided drug discovery approach finds calcium sensitizer of cardiac ... Kleerekoper Q, Putkey JA (Aug 1999). "Drug binding to cardiac troponin C". The Journal of Biological Chemistry. 274 (34): 23932 ...
Qadir MI, Parveen A, Ali M (October 2015). "Cdc42: Role in Cancer Management". Chemical Biology & Drug Design. 86 (4): 432-9. ... Zins K, Gunawardhana S, Lucas T, Abraham D, Aharinejad S (2013-01-01). "Targeting Cdc42 with the small molecule drug AZA197 ...
Drug Design. 86 (4): 410-423. doi:10.1111/cbdd.12527. PMID 25643871. Kaur, Ramandeep; Ranjan Dwivedi, Ashish; Kumar, Bhupinder ... 1,2,4-Triazoles are featured in many kinds of drugs. Notable triazoles include the antifungal drugs fluconazole and ...
Drug Design. 96 (2): 731-744. doi:10.1111/cbdd.13699. ISSN 1747-0285. PMID 32356312. "Amebiasis (amebic dysentery)". ... Treatment includes antimalarial drugs, however, resistance has been observed. New vaccines are being discovered to this day. ... Drug therapy, using Eflornithine and Melarsoprol Pentamidine for T. gambiense and Suramin(Antrypol) for either Trypanosoma ... The severity of the infection can be lessened by treatment with antiprotozoal drugs like buparvaquone. Toxoplasma causes ...
Huczynski, Adam (2012). "Salinomycin - A New Cancer Drug Candidate". Chemical Biology & Drug Design. 79 (3): 235-238. doi: ... "Narasin , Anticoccidial drugs , Drugs , Various , Poultrymed". Muñoz-Planillo, Raúl; Kuffa, Peter; Martínez ... These drugs act as ionophores by binding to ergosterol in the fungal cell membrane and making it leaky and permeable for K+ and ... Chloroquine is an antimalarial and antiamebic drug. It is also used in the management of rheumatoid arthritis and lupus ...
Drug Design. 69 (4): 269-79. doi:10.1111/j.1747-0285.2007.00475.x. PMC 7188353. PMID 17461975.CS1 maint: uses authors parameter ... as well as modelling of enzymatic reactions along with designing novel drugs and chemical compounds of desirable activity with ... in the context of drug design, can a fluorine atom successfully substitute a hydroxyl group?". International Journal of Quantum ... Quantum and classical mechanics computational methods in computer-aided drug design. Dr Wojciech Jankowski (2017), dissertation ...
Drug Design. 95 (2): 205-214. doi:10.1111/cbdd.13626. ISSN 1747-0285. PMID 31571371. S2CID 203622611. Danielson, Jennifer (2011 ... "Treating Obesity:Drug Treatment for Obesity". Treating Obesity. Medscape News. Retrieved March 22, 2012. Franson, K.; Rossner ( ... Lipase inhibitors can be found naturally in plants and can also be produced as pharmaceutical drugs. Some lipase inhibitors ... Overall, orlistat has been considered to be safer than other anti-obesity drugs. Because Lipase inhibitors interferes with the ...
70% of sufferers saw a 50% or more reduction in their migraines following combined neurotherapy and drug treatment, as opposed ... adapted Toomim's system for migraines in 2002 by integrating peripheral thermal biofeedback into the design. Since then, both ... allowing the patient to greatly reduce the drug therapy necessary for him to function successfully in school and offering a ... to 50% undergoing only traditional drug therapy.[8] Autism[edit]. The term autism encompasses a wide range of syndromes, such ...
Label directions are designed to maximize the effectiveness of the product, while protecting the applicator, consumers, and the ... Under Section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), the EPA can also regulate the amount of pesticide ... any nitrogen stabilizer, except that the term "pesticide" shall not include any article that is a "new animal drug" within the ... Drug, and Cosmetic Act"(FDCA).[2] The applicant must provide scientific data from any combinations of over 100 different tests ...
Reunion 5 was announced[8] on September 1997 and saw the introduction of drag and drop capabilities when working with the ... design, allowing index and source windows to remain open for easier access. ... New features include web searching, mapping of places, a tree view, a nav bar and a sidebar, image dragging from a web browser ...
De Smet, Peter A.G.M. (December 1997). "The Role of Plant-Derived Drugs and Herbal Medicines in Healthcare". Drugs. 54 (6): 801 ... These studies tend to have a variety of problems, such as small samples, various biases, poor research design, lack of controls ... 2006). "Drug-related hepatotoxicity". New England Journal of Medicine. 354 (7): 731-39. doi:10.1056/NEJMra052270. PMID 16481640 ... The U.S. Food and Drug Administration (FDA), has issued online warnings for consumers about medication health fraud.[157] This ...
... a move that allowed Pol Pot to focus on the war effort and which was perhaps also designed to improve the Khmer Rouge's image.[ ... "Pol Pot 'killed himself with drugs'". The Guardian. Retrieved 8 August 2014 ...
Resulting information can be used to build biological models, design experiments, or get up to speed in an area of research. ... IPA also lets researchers search for information on genes, proteins, chemicals, drugs, and reagents. ... Food and Drug Administration to use IPA in review of Pharmacogenomics Submissions" (Press release). Ingenuity Systems. June 21 ... US Food and Drug Administration adopts IPA to review pharmacogenomics submissions 2006 - Ingenuity enters into partnerships ...
Designed to span the gap between the coverage provided by the blanket policy written for the entire neighborhood or building ... Subsidence, drag or landslip. *Breakage of glass or sanitary fittings. *Damage from escaped water or oil ... The remainder had the HO-6 Unit-Owners policy, also known as a condominium insurance, which is designed for the owners of ... Fortunately, the "broad form" is designed to cover the most common forms of property damage. ...
... "fourteen drugs were found in Elvis' system, with several drugs such as codeine in significant overprescribed quantities.[20] ... "Elvis' Custom-Designed Planes Will Remain at Graceland". Rolling Stone. Archived from the original on August 22, 2017. ... Constructed at the top of a hill, in a grove of oaks, with rolling pastures surrounding, the house designed by Memphis ... The sitting area has a floor-to-ceiling shatterproof window designed to watch the many racquetball games that took place there ...
... drug occupancy at a purported site of action can be inferred indirectly by competition studies between unlabeled drug and ... PET scanners designed specifically for imaging rodents, often referred to as microPET, as well as scanners for small primates, ... Pharmacokinetics: In pre-clinical trials, it is possible to radiolabel a new drug and inject it into animals. Such scans are ... PC-I was the first instrument using this concept and was designed in 1968, completed in 1969 and reported in 1972. The first ...
Thus, leaf design may involve compromise between carbon gain, thermoregulation and water loss on the one hand, and the cost of ... Strong wind forces may result in diminished leaf number and surface area, which while reducing drag, involves a trade off of ... allowing a degree of repositioning to minimize drag and damage, as opposed to resistance. Leaf movement like this may also ...
The earliest explanation, by the prehistorian Abbe Breuil, interpreted the paintings as a form of magic designed to ensure a ...
Results from Two Identically Designed, Phase 3, Randomized, Double-Blind Clinical Trials". Journal of Drugs in Dermatology. 17 ... "Drug Trials Snapshots: Aklief". U.S. Food and Drug Administration (FDA). 11 October 2019. Archived from the original on 19 ... Aslam I, Fleischer A, Feldman S (March 2015). "Emerging drugs for the treatment of acne". Expert Opinion on Emerging Drugs. 20 ... Aslam I, Fleischer A, Feldman S (March 2015). "Emerging drugs for the treatment of acne". Expert Opinion on Emerging Drugs ( ...
JEL: M54 - Labor Management (team formation, worker empowerment, job design, tasks and authority, job satisfaction). JEL: M55 ... JEL: L65 - Chemicals; Rubber; Drugs; Biotechnology. JEL: L66 - Food; Beverages; Cosmetics; Tobacco. JEL: L67 - Other Consumer ...
... by drugs known as neurokinin type 1 antagonists (also termed: SP antagonists, or tachykinin antagonists.) One such drug is ... The failure of clinical proof of concept studies, designed to confirm various preclinical predictions of efficacy, is currently ... Muñoz M, Rosso M, Coveñas R (Jun 2011). "The NK-1 receptor: a new target in cancer therapy". Current Drug Targets. 12 (6): 909- ... The actions of aprepitant are said to be entirely central, thus requiring passage of the drug into the central nervous system.[ ...
Is electrical brain stimulation used (like drugs) to produce pleasures in humans in other settings than scientific experiments? ... by design, it's not), so there is no charge, but still voltage. PiusImpavidus (talk) 09:04, 3 August 2021 (UTC) ... 1.1 Is electrical brain stimulation used (like drugs) to produce pleasures in humans in other settings than scientific ...
Derby, C. D. (2014). "Cephalopod Ink: Production, Chemistry, Functions and Applications". Marine Drugs. 12 (5): 2700-2730. doi: ... Ancient seafaring people were aware of the octopus, as evidenced by certain artworks and designs. For example, a stone carving ... "designed" to detach during copulation. In 1856 the Danish zoologist Japetus Steenstrup demonstrated that it is used to transfer ...
Pharmacology is the study of drugs and their actions.. *Photobiology is the study of the interactions between non-ionizing ... Medical equipment - Equipment designed to aid in the diagnosis, monitoring or treatment of medical conditions ... of Essential Drugs and Medicines Policy (2002). "Traditional medicine: growing needs and potential". World Health Organization. ... Medications (Rx): what drugs the patient takes including prescribed, over-the-counter, and home remedies, as well as ...
The EF Scale was designed so that a tornado rated on the Fujita scale would receive the same numerical rating, and was ... That begins when increasing rainfall drags with it an area of quickly descending air known as the rear flank downdraft (RFD). ... and the overpass itself was of a unique design.[116] Due to the Venturi effect, tornadic winds are accelerated in the confined ... This downdraft accelerates as it approaches the ground, and drags the supercell's rotating mesocyclone towards the ground with ...
Drug Testing and Analysis. 11 (1): 140-156. doi:10.1002/dta.2471. hdl:10072/382912. PMID 30109771.. ... "best-designed" studies concluded that smoking bans did not harm businesses.[88] Similarly, a 2014 meta-analysis found no ... Drug and Alcohol Review. 37 (7): 912-921. doi:10.1111/dar.12848. PMID 30051520.. ... "What a drag … Iceland considers prescription-only cigarettes". The Guardian. Guardian News. Retrieved 14 March 2014 ...
Designed by architects Peter Eisenman of New York and Richard Trott of Columbus, the center was funded in large part by Ohio ... and alcohol and other drug education.[53] ... Part of its design was to pay tribute to the armory that ... Knowlton Hall was designed by Mac Scogin Merril Elam from Atlanta along with WSA Studio from Columbus, Ohio, and is home to the ... Its design has also been criticized as proving less than ideal for many of the art installations it has attempted to display. ...
A certification test is required to show that a new aircraft design will still take off safely with the tail dragging on the ... The on-ground angle of attack of the wing has to be established during the design phase. The main and nose-gear leg lengths are ...
American chiropractors found that a slight majority favored allowing them to write prescriptions for over-the-counter drugs.[37 ...
The Brabham BT55 was a Formula One racing car designed by Gordon Murray and David North for the Brabham team owned by Bernie ... The aerodynamic concept worked, in that the car produced plenty of downforce without increasing drag which allowed the cars to ... As part of a team headed by Steve Nichols, he played a small part in the design of the very successful McLaren MP4/4 used in ... Murray's next car (which he helped Steve Nichols design), McLaren's MP4/4, is usually claimed to be based on the same ...
U.S. Food and Drug Administration. Retrieved 2010-10-15.. *^ "Title 21-Food and drugs: Chapter i-Food and drug administration: ... "Embedded Systems Design. Retrieved 2016-04-21.. *^ FDA (2010-09-08). "Infusion Pump Software Safety Research at FDA". FDA. ... U.S. Food and Drug Administration. Retrieved 2010-10-15.. *^ a b c d e f "General and Special Controls". Medical Devices. U.S. ... United States (Food and Drug Administration)Edit. Section 201(h) of the Federal Food Drug & Cosmetic (FD&C) Act[6] defines a ...
The design of the CoT incorporated the result of research conducted in the aftermath of Earnhardt's death.[42] All of the ... colliding with Schrader and dragging his car up the track. Earnhardt collided head-on into the retaining wall at a critical ... The separation of the left lap belt was not a result of design or manufacturing defect, but caused by improper installation. ... The belts were of high quality in workmanship and there were no design or manufacturing defects. ...
... offering rewards to anyone who can design a robot to do their job or develop methods to prolong life. Eventually Unistat ... Sex, Drugs and Magick (1973). *The Book of the Breast (1974). *Cosmic Trigger I: The Final Secret of the Illuminati (1977) ...
The rest of the body is shaved for less drag in the water. Others express skepticism at this theory, instead citing the French ... a program designed for testing dogs with flushing capabilities.[37][38][39] Typically, a Miniature Poodle will be the smallest ...
... a drug user, possibly a drug seller, and married to an angry, ungrateful black woman.[30] Obama was accused of dog-whistling to ... several writers criticized Hillary Clinton's campaign's reliance on code words and innuendo seemingly designed to frame Barack ...
The buildings utilize a simple "foursquare" design.[49][56]:56[57] The residential portion of the property has eight "sections ... Many social problems associated with poverty from crime to drug addiction have been prevalent in the area for decades. Despite ... The development was designed by Herman Jessor, organized in the towers in the park layout. ...
Patients undergoing chemotherapy are administered drugs designed to kill tumor cells. Although chemotherapy may improve overall ... The toxicity and many side effects of the drugs, and the uncertain outcome of chemotherapy in brain tumors puts this treatment ... it is not always used to treat brain tumors as the blood-brain barrier can prevent some drugs from reaching the cancerous cells ...
Our internationally renowned speakers will also discuss the latest developments in drug design, including anti-target modelling ... Kinase 2021: 9th RSC / SCI symposium on kinase inhibitor design. 5 July 2021 09:00 - 6 July 2021 17:00, London, United Kingdom ... This website has been designed for modern browsers. To experience its full functionality please enable JavaScript. Without ... The congress features presentations on lead optimisation, structure-activity relationships and fragment-based drug discovery. ...
... peptides have once again become central to the development of new drugs. In Peptide-Based Drug Design: Methods and Protocols, ... Comprehensive and up-to-date, Peptide-Based Drug Design: Methods and Protocols shows its subject to be an independent science ... In Peptide-Based Drug Design: Methods and Protocols, expert researchers provide a handbook which offers a selection of research ... Due to their high specificity and low toxicity profile, peptides have once again become central to the development of new drugs ...
... Case of Malaria Disease Supervision by Assoc.Prof.Im… ... Rational Drug Design using Genetic Algorithm * 1. Final Year project Rational Drug Design Using Genetic Algorithm Case of ... 3. Introduction How a drug works and how we can expect the body to respond to the administration of a drug? Drug design is ... 5. Rational drug design approach(rdda)Foundation of drug design and discovery.Answer the question , which molecule fit best ...
... including necklaces that display the molecular structures of drugs, an alternative drug-testing method and the interior of a ... House of Smart drugs shop by Maurice Mentjens features maze-like wooden beams. Dutch Design Week 2015: design agency Maurice ... drugs. *. Contraceptive jewellery offers alternative method of birth control. Contraceptives and other drugs could be ... Will Patricks Farma bioreactor could let owners brew their own drugs. MIT Media Lab graduate Will Patrick has designed a ...
... with new topics such as pro-drugs, active metabolites and transporters covered in detail in a manner useful to the Drug ... The authors discuss the parameters and processes important for the absorption, distribution and retention of drug compounds in ... the book relates physicochemistry and chemical structure to pharmacokinetic properties and ultimately drug efficacy and safety. ... particularly where drug metabolism impacts on the design of more efficacious and safer drugs.. Charlotte Allerton obtained her ...
... Chapter 3. Replica Exchange Molecular Dynamics Toolkit for Drug-receptor Docking. M. Ito , T. Nishikawa and U. ... Freeze-fracture Electron Microscopy on Nanostructures for Drug & Gene Delivery. B. Papahadjopoulos-Sternberg. NanoAnalytical ...
The term drug design describes the search of novel compounds with biological activity, on a systematic basis. In its most ... Talevi A. (2018) Computer-Aided Drug Design: An Overview. In: Gore M., Jagtap U. (eds) Computational Drug Discovery and Design ... identification of active scaffolds should be conceptually separated from drug design. Traditionally, the drug design process ... Nicolaou CA, Brown N (2013) Multi-objective optimization methods in drug design. Drug Discov Today Technol 10:e427-e435CrossRef ...
... to be sued in state court for a drugs design defects if federal officials approved the brand-name version the generic drug ... The Supreme Court seemed skeptical Tuesday of allowing generic drug manufacturers ... The Supreme Court seemed skeptical Tuesday of allowing generic drug manufacturers to be sued in state court for a drugs design ... Mutual and the Obama administration want that protection extended to the design of the drug, since the generic is an exact copy ...
... 12 October 2016 10:00-16:30, Cambridgeshire, United Kingdom ... Cheminformatics is a dynamic and rapidly evolving field which is at the heart of modern drug design. This forum will allow ... Topics for discussion will include decision-making using data and models, drug design tools for medicinal chemists, software ... Synthesis in Drug Discovery and Development. 26 March 2021 09:00-17:00, Stevenage, United Kingdom. ...
Computers Aid Drug Design and Discovery. By Vidhya Iyer. Mar. 12, 2004 , 10:00 AM. ... Accompanying this progress has been a growing reliance of experimental researchers on computer-aided drug design (CADD). CADD, ... This demonstrates the numerous opportunities for data mining, designing drug candidates, developing models to predict ... the synergy between experimental and computational approaches to drug design can significantly advance the discovery process. ...
Health and medicine/Pharmacology/Drug development/Drug design * /Health and medicine/Clinical medicine/Medical treatments/Drug ... Drug design success propels efforts to fight HIV with a combination of 2 FDA-approved drugs. University of Minnesota Academic ... Drug design success propels efforts to fight HIV with a combination of 2 FDA-approved drugs Peer-Reviewed Publication ... School of Dentistry and Center for Drug Design has developed a new delivery system for a combination of two FDA approved drugs ...
Advances and Progress in Drug Design 17-18 February 2014 Marriott Regents Park Hotel, London UK ... "SMi has a long tradition of organising Advances and Progress in Drug Design that is a high-level, well-organised event ... Advances and Progress in Drug Design taking place on 17-18 February 2014, London UK.. ... dedicated to actual challenges and potential solutions related to rational drug design." Hungarian Academy Of Sciences. ...
The authors therefore suggest that glucocorticoid drugs designed to selectively target the glucocorticoid receptor and not LXR- ... Glucocorticoid drugs are used widely to treat numerous conditions, including rheumatoid arthritis, allergic reactions, asthma, ... The beneficial effects of these drugs are their potent antiinflammatory and immunosuppressive properties. However, their long- ... has now shown that the protein LXR-beta is required in mice for glucocorticoid drugs to elicit many of their negative side ...
9:50 EVOLUTIONARY ALGORITHMS FOR DRUG DESIGN. Dr John Nicholas, Associate Director, Computational Drug Design, Neurion ... new algorithms for design, reducing the drug candidate attrition rate, Novel Protein Kinase Inhibitors: SMART drug design ... 9:10 STRUCTURE-BASED DRUG DESIGN. Dr Michael Hennig, Vice Director & Head, Molecular Structure & Design, Roche *Fragment-based ... 10:50 CHEMOINFORMATICS TOOLS FOR STRUCTURE-BASED DRUG DESIGN. *A fragmented informatics set up - the bane of efficient drug ...
One tactic for combating the spread of drug-resistant strains is to use multiple drugs, such as the combination of dalfopristin ... A comparison of this complex with that of quinupristin bound to the 50S ribosomal subunit may guide design efforts aimed at ...
This volume covers several aspects of rational drug design such as synthesis of novel bioactive drugs development. Chapters ... This volume covers several aspects of rational drug design, such as synthesis of novel bioactive drugs; development and ... Authoritative and cutting-edge, Rational Drug Design: Methods and Protocols aims to ensure successful results in the further ... Rational Drug Design. Methods and Protocols. Editors: Mavromoustakos, Thomas, Kellici, Tahsin F. (Eds.) ...
... derivatives with inhibitory activity toward beta-amyloid aggregation and formation as disease-modifying anti-Alzheimer drug ...
Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors: new disease-modifying agents ... Tacrine-based dual binding site acetylcholinesterase inhibitors as potential disease-modifying anti-Alzheimer drug candidates. ... derivatives with inhibitory activity toward beta-amyloid aggregation and formation as disease-modifying anti-Alzheimer drug ...
Marco-Contelles, J, Leon R, de los Rios C, Samadi A, Bartolini M, Andrisano V, Huertas O, Barril X, Luque FJ, Rodriguez-Franco MI et al.. 2009. Tacripyrines, the first tacrine-dihydropyridine hybrids, as multitarget-directed ligands for the treatment of Alzheimers disease. Journal of medicinal chemistry. 52(9):2724-2732. Abstract ...
We investigate the parameters that can affect protein binding of drugs, as only the unbound fraction is thought to be important ... we are also evaluating the activity of original compounds originally designed as inhibitors of efflux but showing much broader ...
The book also explores the interface between pharmaceutical technology and physiological principles in drug design, a field of ... It discusses a range of concepts for drug delivery systems, treating the routes of drugs with regard to their characteristics: ... This is a review of the structure and function of biological membranes and other cellular barriers used in drug transport. ... Drug Targeting And Delivery: Concepts In Dosage Form Design. Ellis Horwood Series in Pharmacological Sciences. Ellis Horwood ...
... structure-based drug design.[3]. Ligand-basedEdit. Ligand-based drug design (or indirect drug design) relies on knowledge of ... Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new ... the recent focus on rational drug design may limit the progress of drug discovery. Furthermore, the rational design of a drug ... Computer-aided drug design Edit. The most fundamental goal in drug design is to predict whether a given molecule will bind to a ...
... designing drugs (i.e., pharmaceuticals) out of knowledge of the structure and function of proteins. Pioneered a... ... rational drug design (idea). See all of rational drug design, no other writeups in this node. ... Rational drug design can only be understood in the context of the traditional drug discovery process used by large ... A process of synthesizing or "designing" drugs (i.e., pharmaceuticals) out of knowledge of the structure and function of ...
Topics include rational drug design, NMR techniques in drug design, conformational analysis by… ... in studies of the design, structure, mechanism, and actions of pharmaceutical agents. ... NMR in Drug Design discusses the use of nuclear magnetic resonance (NMR) ... Topics include rational drug design, NMR techniques in drug design, conformational analysis by NMR, macromolecular structure ...
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Based Drug Design by Paul Leff from Waterstones today! Click and Collect from your local Waterstones or get FREE UK delivery on ... Receptor-Based Drug Design. introduces novel computer-assisted strategies for the design of new agonists, antagonists, and ... Receptor - Based Drug Design (Paperback). Paul Leff (editor) Sign in to write a review ... Written by over 25 international authorities and containing nearly 1200 bibliographic citations, Receptor-Based Drug Design is ...
... which allows drug elution into the coronary wall for weeks after stent implantation. Category Drug-eluting stents (DES), ... Drug-eluting stents (DES) are coated with an antiproliferative drug, ... Design Features. Drug-eluting stents (DES) are balloon-mounted, expandable, slotted tubular or multilink scaffolds constructed ... encoded search term (Coronary Drug-Eluting Stent) and Coronary Drug-Eluting Stent What to Read Next on Medscape. Related ...
Enzyme Induction and Drug Design Enzyme Inhibition and Drug Design PREDICTING HUMAN PHARMACOKINETICS Objectives of Predicting ... Development of the Unbound (Free) Drug Model. Unbound Drug and Drug Action Unbound Drug Model and Barriers to Equilibrium ... Oxidative Metabolism and Drug Design. Nonspecific Esterases Prodrugs to Aid Membrane Transfer Enzymes Catalyzing Drug ... Reactive Metabolite Screening in Drug Discovery Structural Alerts/Toxicophores in Drug Design. Dealing with Reactive Metabolite ...
Increasing a drugs heft by attaching a larger molecule, called a drug carrier, could help chemotherapy drugs to penetrate ... But how to design these drug complexes to optimize their movement through the tumors… ... Chemotherapy drugs wash in and out of tumors quickly and end up attacking healthy tissues. ... Increasing a drugs heft by attaching a larger molecule, called a drug carrier, could help chemotherapy drugs to penetrate ...
Interactions, Functions and Drug Design. Authors. * Ariel Fernandez Stigliano Copyright. 2015. Publisher. Springer ... On the basis of this information, a multi-disciplinary approach is used to engineer therapeutic drugs and to allow substantive ... Wrapping Drug Combinations for Therapeutic Editing of Side Effects: Systems Biology Meets Wrapping Technology ... Multitarget Control of Drug Impact: A Therapeutic Imperative in Cancer Systems Biology ...
  • Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. (
  • In contrast to traditional methods of drug discovery (known as forward pharmacology), which rely on trial-and-error testing of chemical substances on cultured cells or animals, and matching the apparent effects to treatments, rational drug design (also called reverse pharmacology) begins with a hypothesis that modulation of a specific biological target may have therapeutic value. (
  • SMi has a long tradition of organising Advances and Progress in Drug Design that is a high-level, well-organised event dedicated to actual challenges and potential solutions related to rational drug design. (
  • Authoritative and cutting-edge, Rational Drug Design: Methods and Protocols aims to ensure successful results in the further study of this vital field. (
  • See all of rational drug design , no other writeups in this node. (
  • Rational drug design can only be understood in the context of the traditional drug discovery process used by large pharmaceutical companies, a.k.a. (
  • Topics include rational drug design, NMR techniques in drug design, conformational analysis by NMR, macromolecular structure determination, protein-ligand interactions, drug-DNA interactions, and studies of enzyme mechanisms by NMR. (
  • Employing a wide range of examples from G-protein-coupled receptors and ligand-gated ion channels, this detailed, single-source reference illustrates the principles of pharmacological analysis and receptor classification that are the basis of rational drug design. (
  • Within the scope of rational drug design computational methods gain more and more importance to design workflows that are faster, more efficient and cheaper. (
  • As a replacement to animal models for drug development, organs-on-a-chip has been evaluated for many advantages and disadvantages and has shown a very wide range of applications in organ research and rational drug design. (
  • A method of rational drug design includes simulating polypeptides in a way that predicts the most probable secondary and/or tertiary structures of a polypeptide, e.g., an oligopeptide, without any presumptions as to the conformation of the underlying primary or secondary structure. (
  • Eminent scientists write contributions on all areas of rational drug design and drug discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. (
  • In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it. (
  • In addition to small molecules, biopharmaceuticals including peptides and especially therapeutic antibodies are an increasingly important class of drugs and computational methods for improving the affinity, selectivity, and stability of these protein-based therapeutics have also been developed. (
  • In some cases, small molecules will be designed to enhance or inhibit the target function in the specific disease modifying pathway. (
  • Small molecules (drugs) can be designed so as not to affect any other important "off-target" molecules (often referred to as antitargets) since drug interactions with off-target molecules may lead to undesirable side effects. (
  • Most commonly, drugs are organic small molecules produced through chemical synthesis, but biopolymer-based drugs (also known as biopharmaceuticals) produced through biological processes are becoming increasingly more common. (
  • The search for small molecules that bind to the target is begun by screening libraries of potential drug compounds. (
  • CDSs are biologically inert molecules intended to enhance drug delivery to a particular organ or site and requiring several conversion steps before releasing the active drug. (
  • But the optimal design of these carrier molecules has been under debate. (
  • Molecular Modeling in Drug Design" Molecules 24, no. 2: 321. (
  • The other is the interaction between small molecules and their large, macromolecular receptors, for the development of methodologies for structure-based drug design. (
  • In order to do this, the researchers needed the drug to crystallize with the receptor, but with large receptor molecules, this is not always possible. (
  • In the search for new drug molecules, Numerate uses a statistical method similar to the way Amazon figures out what new books you'll like based on the data it compiles about your past purchases. (
  • Numerate screens big libraries of chemical tests and other data to predict whether a family of compounds is likely to bind to a drug target such as the defective huntingtin protein, based on the compounds' track record of affinity to other molecules. (
  • Most drugs are small molecules. (
  • Chemist Heather Carlson, Ph.D., of the University of Michigan's College of Pharmacy will oversee the creation and operation of the new Community Structure-Activity Resource, which will include detailed molecular information about proteins that bind small, drug-like molecules called ligands. (
  • It includes applications of cyclotides and cyclotide-like molecules as peptide-based drug leads and diagnostic agents. (
  • We explore a new approach in the rational design of specificity in molecular recognition of small molecules based on statistical-mechanical integral equation theory of molecular liquids in the form of the three-dimensional reference interaction site model with the Kovalenko-Hirata closure (3D-RISM-KH). (
  • To accomplish this, many drug molecules are composed of units called fragments that are linked through chemical bonds. (
  • By highlighting some of the general principles involved in taking molecules through basic science to clinical development, this book offers a complete and authoritative reference on the design and discovery of anticancer drugs for translational scientists and clinicians involved in cancer research. (
  • Nanocarriers can be designed with molecules on their exteriors that only bind to biomarkers found on a certain type of cell. (
  • Design of Hybrid Molecules for Drug Development reviews the principles, advantages, and limitations involved with designing these groundbreaking compounds. (
  • Beginning with an introduction to hybrid molecule design and background as to their need, the book goes on to explore a range of important hybrids, with hybrids containing natural products, molecules containing NO- and H2S-donors, dual-acting compounds acting as receptor ligands and enzyme inhibitors, and the design of photoresponsive drugs all discussed. (
  • Drawing on practical case studies, the hybridization of molecules for development as treatments for a number of key diseases is then outlined, including the design of hybrids for Alzheimer's, cancer, and malaria. (
  • His predominant focus is on the design of novel therapeutic compounds for the treatment of Alzheimer's disease, which has led his group to a particular interest in the design of hybrid molecules. (
  • The startup not only scouts for new drug sites using its AI and deep learning platforms but also develops novel molecules to target them. (
  • And how we achieve this is to work around this design, make test iterative cycle where we identify new molecules to make, we enumerate those molecules in the computer. (
  • We also have to adapt the process to molecules that could be used directly for drug development. (
  • Furthermore, in vitro experiments complemented with computation methods are increasingly used in early drug discovery to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological profiles. (
  • These approaches represent systematic methodologies that thoroughly integrate structure-activity (SAR) and structure-metabolism (SMR) relationships and are aimed at designing safe, locally active compounds with improved therapeutic index (ratio of benefit vs. side effect). (
  • Bodor defined soft drugs as biologically active, therapeutically useful chemical compounds characterized by a predictable and controllable in vivo metabolism to non-toxic moieties after they achieve their therapeutic role. (
  • There are also compounds that can be considered as soft chemicals (e.g., malathion) or soft drugs (e.g., articaine, methylphenidate) even though they were not developed as such. (
  • The authors discuss the parameters and processes important for the absorption, distribution and retention of drug compounds in the body, plus the potential problems created by their transformation into toxic byproducts. (
  • The term drug design describes the search of novel compounds with biological activity, on a systematic basis. (
  • Kohn has collaborated with Tropsha to develop a new series of anti-epileptic drugs that could be even more powerful than one of his earlier discovered compounds. (
  • In collaboration with the team of JM Bolla at the Université Aix-Marseille (France), we are also evaluating the activity of original compounds originally designed as inhibitors of efflux but showing much broader synergistic effects with antibiotics, in our models of infections, including intracellular infections and activity against strains that show resistance to other antibiotic classes or mutations in their efflux systems. (
  • A concise introduction to the parameters and processes governing the absorption, distribution and retention of drug compounds in the body, now expanded to cover prodrugs, antitumor drugs and predictive approaches. (
  • This pharmacophore pattern can be derived from the 3D maximum common substructure (3D-MCSS) that these compounds have in common and it can help finding new lead structures necessary for drug design in medicinal chemistry (Figure 1). (
  • These ligands may warrant further study as so-called lead compounds for drug discovery. (
  • The ability to screen compounds and accurately predict their binding properties using only computers would greatly impact the drug development process and many other aspects of biomedical research. (
  • A team of MIT chemists has devised a new way to add fluorine to a variety of compounds used in many drugs and agricultural chemicals, an advance that could offer more flexibility and potential cost-savings in designing new drugs. (
  • Computer-aided drug design (CADD) is an interdisciplinary subject, playing a pivotal role during new drug research and development, especially the discovery and optimization of lead compounds. (
  • Clearly though, a clinical trial is required next to tell us whether this drug or similar compounds are both effective and safe in hair loss patients. (
  • On one hand, conventional methods for drug discovery involve the costly random screening of synthesized compounds or natural products. (
  • The rational design of novel compounds, useful as drugs, e.g., bioactive peptidomimetic compounds, and constrained analogs thereof, is thus made possible using the simulation methods and tools of the described invention. (
  • However, compounds made up entirely of "Y drugs" are treated as approved medications and don't require preauthorization. (
  • We saw an immediate decrease in 'N drug' compounds in Texas" when its closed formulary went into effect in 2011, said Brian Allen, Westerville, Ohio-based vice president of government affairs at pharmacy benefit manager Helios. (
  • But what we have since seen is a commensurate spike in compounds that are all 'Y drugs. (
  • In Texas, 'Y drug' compounds are subject to retrospective review, which means "they're getting through the system and sometimes getting paid for before the retrospective review happens," Mr. Allen said. (
  • Oklahoma's formulary, which is to expire in September, treats all compounds as 'N drugs, 'Mr. Allen said. (
  • So if (formularies) treat compounds like 'N drugs,' then it can have an impact. (
  • Molecular modeling and medicinal chemistry-based design, synthesis, evaluation and delivery of novel anti-microbial, anti-malarial, anti-cancer and anti-inflammatory compounds. (
  • The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. (
  • A more accurate term is ligand design (i.e., design of a molecule that will bind tightly to its target). (
  • With the rise of biotechnology and fast computers it became possible to approach the problem in a different way: try to build a molecule from scratch that can attack your drug target. (
  • Above a certain size, a molecule can't be absorbed into the bloodstream through the stomach, and has to be injected , which is a drag, requires a medical professional , and limits the marketability of the drug. (
  • Increasing a drug's heft by attaching a larger molecule, called a drug carrier, could help chemotherapy drugs to penetrate deeply into tumors - and stay there. (
  • Under current methods, a pharmaceutical company might synthesize hundreds of small molecule drug candidates and laboriously test each in lab assays, in a "trial and error" quest to weed out the best prospects, says Numerate CEO Guido Lanza. (
  • This made it especially interesting as a target molecule for new drugs. (
  • While most of their methods and examples come from the area of pharmaceutical discovery and development, the approaches are equally applicable for chemical probes and diagnostics, pesticides, and any other molecule designed to interact with a biological system. (
  • St. Jude Children's Research Hospital scientists have identified a small, drug-like molecule that inhibits the function of a "disordered" protein in research that may advance a novel approach to hearing restoration. (
  • Free drugs are cleared from articular joints in a matter of hours to days, with some dependence on the molecular weight of the drug molecule. (
  • Changing the molecule or the device design cannot be done without FDA approval, so preemption should apply (even if courts often miss this point). (
  • An ideal drug molecule for a specific protein disease target should be a combination of fragments that fit into each hot spot in the best possible way. (
  • Before he can begin designing a molecule, Chenglong Li must obtain information about a specific protein target, especially the protein structures. (
  • Cancer Drug Design and Discovery, Second Edition is an important reference on the underlying principles for the design and subsequent development of new anticancer small molecule agents. (
  • Intensive research is underway to try to find anti-AIDS drugs that can block these enzymes, but efforts were hampered by not knowing exactly what the retroviral protease molecule looked like. (
  • Equally amazing, surfaces on the molecule stood out as likely targets for drugs to de-active the enzyme. (
  • Led by Marion Emmert, PhD , assistant professor of chemistry and biochemistry at WPI, the research program involves early-stage technology developed in her lab that may yield a more efficient and predictable method of bonding a vital class of structures called aromatic and benzylic amines to a drug molecule. (
  • First, the drug needs to physically attach or "bind" to the target, which is a specific part of a cell, protein, or molecule. (
  • Although both retrometabolic design approaches involve chemical modifications of the molecular structure and both require enzymatic reactions to fulfill drug targeting, the principles of SD and CDS design are distinctly different. (
  • These necklaces by Canadian studio Ahora Silhouettes display the molecular structures of drugs, allowing the wearer to accessorise with the illicit substance of their choice (+ slideshow). (
  • His research interests include the role of molecular properties in drug disposition and computational modeling of ADMET properties. (
  • Traditionally, the drug design process has focused on the molecular determinants of the interactions between the drug and its known or intended molecular target. (
  • MINNEAPOLIS/ST. PAUL (08/30/2013) - A University of Minnesota research team featuring researchers from the Institute for Molecular Virology, School of Dentistry and Center for Drug Design has developed a new delivery system for a combination of two FDA approved drugs that may serve as an effective treatment for the human immunodeficiency virus (HIV). (
  • Recent advances in drug design, including computational chemistry, combinatorial chemistry and molecular modelling, may have the potential to overcome the shortcomings of conventional approaches and revolutionise drug design methodologies. (
  • For 20 years, chemists have known, in theory at least, that they could take advantage of tumors' leaky blood vessels and nonexistent drainage systems - if they could design and synthesize a drug carrier with the right molecular weight. (
  • On the basis of this information, a multi-disciplinary approach is used to engineer therapeutic drugs and to allow substantive advances in targeted molecular medicine. (
  • Salo-Ahen, O.M.H. Molecular Modeling in Drug Design. (
  • The path toward a breakthrough drug often starts with a new insight about the molecular cause of an illness, but only a few of these discoveries lead to new treatments. (
  • As our understanding of biological processes at both the macroscopic and molecular levels increases in complexity, new approaches and concepts rapidly feed into drug discovery programs, producing new tools that further inform our understanding in an iterative way. (
  • Drug discovery is an early adopter of biochemical innovation, and this 2016 American Society for Biochemistry and Molecular Biology annual meeting symposium will highlight some of the approaches being taken to engage the most recent advances in biochemistry and molecular biology. (
  • Systematically examining current methods and strategies, this ready reference covers a wide range of molecular structures, from organic-chemical drugs to peptides, Proteins and nucleic acids, in line with emerging new drug classes derived from biomacromolecules. (
  • His research activities concentrate on method development for adaptive molecular design and their tight integration with innovative chemical and biophysical techniques in drug discovery. (
  • The last decade has seen tremendous progress in the development of analytical techniques such as mass spectrometry and molecular biology tools, resulting in important advances in drug discovery, particularly in the area of absorption, distribution, metabolism, and excretion (ADME). (
  • The University of Michigan will lead the effort to expand and enhance the molecular data needed to develop computer programs that more accurately predict potential drug candidates. (
  • These data, in conjunction with comparative inhibition kinetics, provide insight into the molecular mechanisms that drive cysteine protease inhibition by vinyl sulfones, the binding specificity of these important proteases and the potential of vinyl sulfones as antiparasitic drugs. (
  • Pharmaceutical research has successfully incorporated a wealth of molecular modeling methods, within a variety of drug discovery programs, to study complex biological and chemical systems. (
  • Broadly used in modern drug design, molecular docking methods explore the ligand conformations adopted within the binding sites of macromolecular targets. (
  • The purpose of this review is to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the advances in the field and the role played by the integration of structure- and ligand-based methods. (
  • ThePTMC-PAA ratio, the molecular weight of the PTMC, andinteractions amongst these factors significantly influenced therelease performance, mass loss and degree of plasticization andthe relationships obtained enabled the erosion and drug releasepattern to be predicted and controlled. (
  • Key factors that regulate the biological activity of thesepolymeric vehicles were identified as drug solubility,composition, molecular weight, stereochemical configuration,and morphology. (
  • Among methods employed in drug discovery, pharmacophore modelling, multi-dimensional quantitative structure activity relationships (such as, 4- and 3D-QSAR), Comparative Molecular Field Analysis (CoMFA), and Comparative Molecular Similarity Indices Analysis (CoMSIA) remain the preferred ligand-based (LB) methods for fast virtual screening (VS) procedures and for rationalizing the activities of a set of ligands. (
  • Molecular Modelling and Structure-based Drug Design, offered by the University of Leeds, is one of a number of online courses run jointly with The University of Manchester. (
  • Scientists are taking the trial and error out of drug design by using powerful computers to identify molecular structures that have the highest potential to serve as the basis for new medications. (
  • Chenglong Li verified that the technique works by comparing a molecular structure he designed to the molecular base of an existing cancer medication that targets a widely understood protein. (
  • Chenglon Li starts the design process with molecular fragments that come from thousands of existing drugs already on the market. (
  • Thorough and accessible, Drug Design and Discovery: Methods and Protocols serve as a vital laboratory reference for pharmaceutical chemists, medicinal chemists, and pharmacologists as well as for molecular biologists. (
  • These features provide exciting opportunities for the design of retroviral drugs, including AIDS drugs,' write Khatib and co-authors of a paper appearing yesterday in the journal Nature Structural & Molecular Biology . (
  • The Pharmaceutical Manufacture and Control course targets industrialists interested in moving newly developed drugs into the mass manufacturing arena, this programme however is aimed at molecular chemists with a passion for drug creation. (
  • Pajouhesh H, Lenz GR (2005) Medicinal chemical properties of successful central nervous system drugs. (
  • This forum will allow medicinal chemists and scientists involved in drug design to meet and discuss the latest developments and best practices. (
  • Topics for discussion will include decision-making using data and models, drug design tools for medicinal chemists, software for sharing ideas and collaboration. (
  • Harold Kohn, Kenan chair of the division of medicinal chemistry and natural products, who has frequently collaborated with Tropsha, says, "The speed of computer-aided drug discovery fits Alex's personality. (
  • Current Computer-Aided Drug Design is an essential journal for all medicinal chemists who wish to be kept informed and up-to-date with all the latest and important developments in computer-aided methodologies and their applications in drug discovery. (
  • Scientists and researchers in drug metabolism, pharmacology, medicinal chemistry, pharmaceutics, toxicology, and bioanalytical science will find ADME-Enabling Technologies in Drug Design and Development an invaluable guide to the entire drug development process, from discovery to regulatory issues. (
  • Letters in Drug Design & Discovery will fill an important niche for the translation of exciting new research in the fields of medicinal chemistry and drug development. (
  • Furthermore, computer-aided drug design (CADD) approaches are important for reducing the experimental use of animals for in vivo testing, for aiding the design of safer drugs, and for repositioning known drugs, assisting medicinal chemists at each step (design, discovery, development, and hit-optimization) during the drug discovery process. (
  • As such, this Research Topic welcomes submissions from researchers in the field of computational drug discovery and design, including original research and review articles related to the in silico approaches used in Medicinal Chemistry. (
  • Hello, I'm Nathan Brown from the Institute of Cancer Research in London, and today I'm going to be talking to you about computational methods in ligand-based drug design for medicinal chemistry. (
  • So we use computational methods to design, select and prioritise synthetic chemistry targets that will then contribute positively to a medicinal chemistry project. (
  • And I'm going to talk to you today about structure-based drug design and the computational methods we apply in developing medicinal chemistry strategies. (
  • We're using computational methods to design, select, and prioritize synthetic chemistry targets that will then contribute positively to the medicinal chemistry project. (
  • In the field of drug discovery, retrometabolic drug design is a strategy for the design of safer drugs either using predictable metabolism to an inactive moiety or using targeted drug delivery approaches. (
  • The concept of retrometabolic drug design encompasses two distinct approaches. (
  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. (
  • This recent success demonstrates that with good experimental backing, the synergy between experimental and computational approaches to drug design can significantly advance the discovery process. (
  • How can we successfully apply ligand-based and structure based computational approaches for the rational design of novel GPCR antagonists? (
  • What are the best approaches in building a robust technology pipeline for robust fragment based drug discovery? (
  • The agenda for 2015 will feature case study driven presentations from an array of market leaders such as the University of Cambridge, Janssen, MedImmune, Sanofi and Novartis, discussing computational approaches, structure based drug design, pharmacokinetics, polypharmacology, drug metabolism and fragment based drug design. (
  • Focussing on drug discovery from key targets and placing an emphasis on the multi-disciplinary approaches necessary to challenge these issues, this book comprehensively covers the new and recent discoveries in the area of carbohydrate drug discovery. (
  • And bringing together a detailed understanding of the enzymology and mechanism of neurodegenerative diseases rapidly is advancing therapeutic approaches using the tools of structure-based design. (
  • C. A. Lipinski, F. Lombardo, B. W. Dominy and P. J. Feeney, "Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings," Advanced Drug Delivery Reviews, Vol. 46, No. 1-3, 2001, pp. 3-26. (
  • Once information about the 3D structure of the targets in complex with ligands has been elucidated, structure-based (SB) drug design approaches like SB pharmacophore models-which include excluded volumes or high throughput dockings-are the elected methods for identifying novel chemical entities for a selected target. (
  • Significant technological gains in hardware and software resources, algorithm design, as well as biological advances in identifying new drug targets, have made computer-assisted approaches the most valuable methods in pre-clinical research. (
  • Research and postgraduate study in the area of drug design, development and delivery can focus on the design of novel therapeutic drugs and new delivery approaches. (
  • Conjugation technologies are also contributing to the growth of peptide therapeutics, and leading to innovative approaches to designing safe and effective therapies. (
  • Potential drug targets are not necessarily disease causing but must by definition be disease modifying. (
  • In: Vaz RJ, Klabunde T (eds) Anti-targets: prediction and prevention of drug side effects. (
  • Special computational techniques are also available to discover biological targets (proteins, nucleic acids) of a drug. (
  • Enzymes take a key role in the research of the pharmaceutical industry, because they represent targets for the specific development of drugs. (
  • Despite the use of intra-articular injection as a technique for local delivery to the joint, free drugs are unable to remain within the joint space for adequate time periods and thereby do not reach their biological targets at sufficient levels (8) . (
  • Drugs that modulate several targets have the potential for an improved balance of efficacy and safety compared to single targets agents. (
  • Although there are a number of marketed drugs that are thought to derive their therapeutic benefit by virtue of interacting with multiple targets, the majority of these were discovered accidentally. (
  • These enzymes have therefore emerged as promising targets for antiparasitic drugs. (
  • With extensive colourful and helpful visualisations, the new resource can help identify and characterise drug targets as well as support the design of new therapeutics for cancer. (
  • The new tool is set to change the way researchers interact with genomic mutations in order to identify new cancer drug targets. (
  • This displays cancer mutations alongside binding sites with predictions of how likely a pocket is to be successful as a drug target, enhancing the exploration and identification of how mutations impact therapeutic targets. (
  • Traditional Chinese Medicine (TCM) modernization is the only way of TCM development and also an effective approach to the development of new drugs and the discovery of potential drug targets (PDTs). (
  • The osteoporosis drug, discovered to work for baldness by the University of Manchester, targets a protein that acts as a brake on hair growth and plays a key role in hair loss. (
  • Remarkable progress has been made both in computer science (accelerating drug discovery research), and the development of new experimental procedures for the characterization of biological targets. (
  • A team of University of Pennsylvania researchers has developed a computer model that will aid in the design of nanocarriers, microscopic structures used to guide drugs to their targets in the body. (
  • While many AI biotech companies are on journeys to discover new drug targets, Hong Kong-based Insilico Medicine is a step ahead. (
  • Using information about the site, it developed potential drug targets. (
  • Insilico will use the funds to start human clinical trials, initiate multiple new programs for novel and difficult targets, and further develop its AI and drug discovery capabilities. (
  • The new drugs thus designed achieve selective organ and/or therapeutic site drug targeting and produce safe therapeutic agents and safe environmental chemicals. (
  • One approach is the design of soft drugs (SDs), new, active therapeutic agents, often isosteric or isolelectronic analogs of a lead compound, with a chemical structure specifically designed to allow predictable metabolism into inactive metabolites after exerting their desired therapeutic effect(s). (
  • He worked for Pfizer for 24 years in the Pharmacokinetics, Dynamics and Metabolism Department contributing scientific leadership to the drug metabolism and pharmacokinetic evaluations on many drug discovery and development projects across a range of therapeutic areas including cardiovascular, allergy and respiratory, anti-infectives and sexual health. (
  • Moreover, articular cartilage, which is often the therapeutic target of disease-modifying drugs, presents a formidable biological barrier to drug delivery. (
  • Diffusion through cartilage is slower than the clearance rate of the joint, so free drug in the joint space is typically cleared before it can penetrate the depth of cartilage at a therapeutic concentration. (
  • Even modest improvements in intra-articular penetration and half-life could have a considerable impact on therapeutic drug exposure time between injections ( Figure 2 ). (
  • Improved drug delivery would extend the residence time of intra-articular drug therapies in joints, which would markedly increase the total time at therapeutic dose over the course of treatment. (
  • For a drug to do its job in the body it must interact with a specific biological target and produce a therapeutic effect. (
  • MIT Media Lab graduate Will Patrick has designed a prototype desktop bioreactor that could enable the production of pharmaceutical drugs at home. (
  • The book also explores the interface between pharmaceutical technology and physiological principles in drug design, a field of increased importance to industry. (
  • NMR in Drug Design discusses the use of nuclear magnetic resonance (NMR) in studies of the design, structure, mechanism, and actions of pharmaceutical agents. (
  • The group had been approached by pharmaceutical companies wanting to know how certain drug leads bind to receptors. (
  • As we noted yesterday, true design claims, as opposed to failure to warn claims, aren't the crux of most pharmaceutical drug cases. (
  • COSMIC-3D has been designed to directly assist pharmaceutical development. (
  • A key resource underpinning cancer genetic research, COSMIC provides large high-quality datasets, methods and graphics to scrutinise the genetics causing this disease, giving insights to pharmaceutical design and patient therapies. (
  • J. Yang, W. Y. Hua and S. X. Peng, "New trend of CADD-Receptor Structure-Based Drug Design," Journal of China Pharmaceutical University, Vol. 24, No. 3, 1993, pp. 187-192. (
  • Letters in Drug Design & Discovery should be available in every library in the pharmaceutical industry and in universities. (
  • Letters in Drug Design & Discovery represents an important review journal of great value to pharmaceutical scientists. (
  • Letters in Drug Design & Discovery is an important new journal to experts and anyone interested in the pharmaceutical sciences from both industry as well as academia. (
  • Lanza says the Huntington's disease work is a welcome shift from using Numerate's platform as a service for large pharmaceutical firms, and instead delving into drug discovery at its own direction. (
  • Train as a pharmaceutical scientist at Liverpool John Moores University on this Masters-level Drug Discovery and Design course. (
  • The book series should prove to be of interest to all the pharmaceutical scientists involved in research in drug design and discovery. (
  • A process of synthesizing or "designing" drugs (i.e., pharmaceuticals) out of knowledge of the structure and function of proteins. (
  • The design of binding sites for nonnatural ligands into natural proteins is a very topical subject in protein design. (
  • Thus, starting from human α1-antichymotrypsin, two drug-binding proteins were developed. (
  • It is proposed that such binding proteins can be further developed into drug-specific delivery shuttles. (
  • While the design of ligand-binding sites into proteins remains challenging, this holds even truer for the coupling of a newly engineered binding site to an allosteric mechanism that regulates the ligand affinity. (
  • The data screening also looks at other traits of the candidate drugs, such as their tendency to form harmful interactions with other proteins. (
  • De novo design of peptides, proteins and nucleic acid structures, including RNA aptamers and many more. (
  • The results also raise broader hopes regarding drug development targeting disordered proteins. (
  • Disordered proteins are implicated in a wide range of diseases, including diabetes and neurodegenerative disorders, but so far drug-development efforts have failed. (
  • Most drugs work by binding to proteins' stable 3-D shape, which disordered proteins lack. (
  • Most drugs work by latching onto proteins and altering a biological process. (
  • We are currently soliciting manuscripts on Computer-Aided Drug Discovery: From Target Proteins to Drug Candidates for the Pacific Symposium on Biocomputing (PSB-99). (
  • Most drugs are designed to act on proteins that somehow malfunction in ways that lead to damage and disease in the body. (
  • Covering both classic and cutting-edge techniques, this volume explores computational docking, quantitative structure-activity relationship (QSAR), peptide synthesis, labeling of peptides and proteins with fluorescent labels, DNA-microarray, zebrafish model for drug screening, and other analytical screening and biological assays that are routinely used during the drug discovery process. (
  • And lastly, we'll move into virtual ligand docking, that's how we can simulate the docking of ligands into proteins and protein binding sites to understand potential interactions that can be exploited in optimizing potency in the drug program. (
  • Nevertheless, due to high attrition rates, especially during clinical phases of drug development, more attention is being focused early in the drug design process on selecting candidate drugs whose physicochemical properties are predicted to result in fewer complications during development and hence more likely to lead to an approved, marketed drug. (
  • Due to their high specificity and low toxicity profile, peptides have once again become central to the development of new drugs. (
  • There are several rationally designed soft drugs that have either already reached the market, such as esmolol (Breviblock) landiolol (Onoact) remifentanil (Ultiva) loteprednol etabonate (Lotemax, Alrex, Zylet) clevidipine (Cleviprex) or are in late-stage development (remimazolam, budiodarone, celivarone, AZD3043, tecafarin). (
  • His research interests and publications span all aspects of drug discovery and development, particularly where drug metabolism impacts on the design of more efficacious and safer drugs. (
  • Raschi E, Vasina V, Poluzzi E, De Ponti F (2008) The hERG K+ channel: target and antitarget strategies in drug development. (
  • According to an article in Word Pharma News, ( ), Bayer announced that they were now accelerating the development of five promising drug candidates which are currently undergoing phase I and II clinical studies. (
  • Our research and development activities are strongly focused on areas where treatment options are not available today or where true breakthrough innovations are missing,' said Prof. Andreas Busch, member of the Bayer HealthCare Executive Committee and Head of Global Drug Discovery at Bayer HealthCare. (
  • The keynote titled: Aligning biochemical and biophysical assays for successful drug discovery, will explore accelerating assay development and expanding assay options for primary screening campaigns. (
  • Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of computational techniques for drug design, screening, ADME studies, etc., providing excellent rationales for drug development. (
  • Steven Finkbeiner at the Gladstone Institutes in San Francisco has uncovered a mechanism behind Huntington's disease, and his lab is now working with the San Bruno, CA, startup Numerate to try to beat the odds in drug development. (
  • A main principle in drug discovery and development is the interaction between receptors and enzymes with their ligands. (
  • ADME-Enabling Technologies in Drug Design and Development focuses on the current state of the art in the field, presenting a comprehensive review of the latest tools for generating ADME data in drug discovery. (
  • However, despite decades of research and development, no disease-modifying drug for osteoarthritis has been approved for use in humans (2) . (
  • If we know the structure of a compound bound to a drug target, we should be able to tell how tightly the compound binds - information critical to drug development. (
  • The ultra-stable cyclotides are promising templates for drug development applications and are currently being assessed for the potential breadth of their applications. (
  • Astex is a leader in innovative drug discovery and development, committed to the fight against cancer and diseases of the central nervous system. (
  • Discovery and validation of PTDs has become the "bottle-neck" restricted new drug research and development and is urgently solved. (
  • J. Yang and W. Y. Hua, "Basic Pharmacophore for Some Antithrombotic Agents with Combined Thromboxane Receptor Antagonists (TXRA)/Thromboxine Synthase Inhibitor (TXSI) Activities," Drug Development Research, Vol. 39, No. 2, 1996, pp. 197-200. (
  • The breakthrough can pave the way for the development of medicine to which bacteria have a significantly slower rate of developing resistance, and help prevent hundreds of thousands of deaths each year caused by drug-resistant bacteria. (
  • The toxicity and proof-of-concept studies have shown that this can be on the drug development pathway as it shows good potency and low toxicity and we look forward to having this developed as a topical drug for humans. (
  • Drug development is a long and costly process which suffers from the major shortcoming that frequently failure is often only determined during the final stage. (
  • To achieve this goal it is essential to implement efficient methods for the design and analysis of such early development studies. (
  • At least one paper by each researcher discussing state of the art statistical methods relevant in medical statistics and drug development for a non-statistical audience and has been submitted to a substantive journals. (
  • These novel clinical trial designs can dramatically increase the cost-effectiveness of drug development, leading to life-altering medicines for people suffering from serious illnesses, possibly at lower cost. (
  • Currently, the cost of drug development is unsustainable. (
  • The first issue of the journal Current Computer-Aided Drug Design is reflective of the course taken by the editor on the broadest possible coverage of the methodology development and applications of modern computational drug discovery. (
  • This is mostly because they can impact the entire drug development trajectory, identifying and discovering new potential drugs with a significant reduction to cost and time. (
  • Novo Nordisk A/S is fashioning its R&D makeover to integrate artificial intelligence across its drug discovery and development process, after a pilot program delivered the cost and time savings the pharma was looking for. (
  • In that transition, Numerate is following in the path of other former drug discovery platform companies such as Exelixis , which shifted to drug development and scored its first FDA approval late last year. (
  • Numerate's efforts for its partners did not lead to any drug candidates in development, Lanza says, but each project "pushed the limits of the technology. (
  • Website development support from Andrew Koyfman with design support from Rob Hunter . (
  • This book includes several sections on the basic and applied science of cancer drug discovery and features those drugs that are now approved for human use and are in the marketplace, as well as those that are still under development. (
  • With its cutting-edge reviews of breaking developments in this exciting field, the book offers a novel approach for all those working in the design, development, and administration of drugs for a range of debilitating disorders. (
  • A Comprehensive Guide to Toxicology in Nonclinical Drug Development. (
  • Basics and Strategies for Drug Discovery and Development. (
  • Our PhD/MPhil Drug Design, Development and Delivery programme enables you to undertake a research project that will improve understanding of Drug Design, Development and Delivery. (
  • Design of new formulations to improve drug stability (stroke treatment), development of lipid-based nanocarriers and new excipients to improve drug delivery (tuberculosis treatment) and penetration of anti-amyloid drugs across the blood-brain barrier. (
  • The work in the laboratory of Marion Emmert will advance a new chemical process for more effective drug development and manufacturing. (
  • The National Institutes of Health (NIH) has awarded $346,000 to Worcester Polytechnic Institute (WPI) for a three-year research project to advance development of a chemical process that could significantly improve the ability to design new pharmaceuticals and streamline the manufacturing of existing drugs. (
  • Tropsha now develops models to test the relation between structure and activity of drug candidates and studies protein folding and the effects of mutations on protein structure. (
  • CADD, or "rational drug discovery," helps make it possible to select a more manageable number of candidates that can then be tested experimentally. (
  • The company plans to progress these five new highly innovative drug candidates in the areas of oncology, cardiology, and women's health into phase III clinical studies by 2015. (
  • 2010. Novel huprine derivatives with inhibitory activity toward beta-amyloid aggregation and formation as disease-modifying anti-Alzheimer drug candidates . (
  • 2010. Tacrine-based dual binding site acetylcholinesterase inhibitors as potential disease-modifying anti-Alzheimer drug candidates . (
  • Promising candidates are refined, the active ingredient is identified, and a drug is born. (
  • Numerate will be looking for drug candidates to block that protein. (
  • The company has been refining its "in silico" method of evaluating drug candidates as an alternative to traditional lab procedures. (
  • His lab will first test the drug candidates on human nerve cells grown in a lab dish, rather than in animals that have been engineered to develop a facsimile of Huntington's disease in humans. (
  • SMi's 15th Annual Drug Design Conference will focus on biophysical techniques to highlight advancements in modelling protein conformations and drug candidates. (
  • This week they published very encouraging results where they describe the exclusive use of bioinformatics software to develop new potential drug candidates against a newly discovered, essential enzyme of the Malaria-inducing parasite, Plasmodium falciparum. (
  • This paper mainly discusses the "druggability" and specificity of PTDs, the "druglikeness" of drug candidates, the methods and technologies of the discovery and validation of PTDs and their application. (
  • The immediate goal is to produce a limited number of lead drug candidates that can be advanced beyond lab tests into early animal studies. (
  • In Peptide-Based Drug Design: Methods and Protocols , expert researchers provide a handbook which offers a selection of research and production tools suitable for transforming a promising protein fragment or stand-alone native peptide into a pharmaceutically acceptable composition. (
  • Contraceptives and other drugs could be administered through an earring, using a method invented by researchers at the Georgia Institute of Technology. (
  • Accompanying this progress has been a growing reliance of experimental researchers on computer-aided drug design (CADD). (
  • A team of researchers, led by Carolyn Cummins, at the University of Toronto, Ontario, has now shown that the protein LXR-beta is required in mice for glucocorticoid drugs to elicit many of their negative side effects. (
  • Researchers at Duke University, led by Ashutosh Chilkoti , associate professor of biomedical engineering, have now generated a wealth of information about how drug carriers move through tumors and what sizes are best for targeting the tumors. (
  • The Duke researchers anesthetized mice, put them on a microscope platform, and injected fluorescently labeled drug carriers into their tail blood vessels. (
  • is a user-friendly online directory of life science companies designed to help scientists and researchers find and obtain the products they need quickly and easily. (
  • This meant sequential regulation was occurring and, next, the researchers have been designing cell biology experiments to verify the physiological meaning of this control. (
  • Researchers at the Uppsala University (Sweden) are using a computer-assisted strategy for rapid drug design for various diseases. (
  • There is a tremendous interest in these enzymes among drug researchers. (
  • Advanced drug delivery systems developed by researchers can make this goal possible. (
  • Singapore, 12 December 2019 - Researchers from Singapore-MIT Alliance for Research and Technology (SMART), MIT's research enterprise in Singapore, and Nanyang Technological University (NTU) have designed an antimicrobial polymer that can kill bacteria resistant to commonly used antibiotics, including the superbug Methicillin-resistant Staphylococcus aureus (MRSA). (
  • While the next step for the research is to test the polymer on animals infected by MRSA in pig farms, the researchers are also preparing to have the drugs tested in clinical trials for use for the public. (
  • Using a cross-sectorial, transnational approach, the IDEAS network brings together leading public and private sector researchers in the field with ample experience in training to educate, promote and support the future leaders in medical statistics in general and in the design and analysis of early developmental studies in particular. (
  • Journal will not only help researchers in the field of structure-activity studies to follow recent advancement in the field but hopefully will also help to bridge the gap between diverse methodologies addressing properties of highly complex interactions of drugs and large biomolecules. (
  • The British researchers first discovered a potential treatment in cyclosporine A - a drug given to patients after organ transplants since the 1980s to suppress their immune system. (
  • This hands-on training will introduce researchers to the concepts, methods and tools for structure and ligand based computational drug designing and discovery using the open source tools and the cloud computing facilities. (
  • The articles published in Drug Designing: Open Access have been cited 22 times by eminent researchers all around the world. (
  • Teams send in their answers, and UW researchers constantly improve the design of the game and its puzzles by analyzing the players' problem-solving strategies. (
  • The article presents information on a clinical research study to be released by Celldex Therapeutics Inc. This study is related to CDX-011, an antibody drug conjugate (ADC) that contains a human monoclonal antibody, in patients with advanced breast cancer. (
  • The article discusses the pivotal study called METRIC by biopharmaceutical company Celldex Therapeutics Inc. as a result of the positive data gathered from its Phase II trial of antibody-drug conjugate (ADC) glembatumumab vedotin (CDX-011) in patients with metastatic, triple-negative breast. (
  • The article informs about the phase IIb trial of CDX-011 antibody drug conjugate by Celldex Therapeutics Inc. in patients expressing glycoprotein NMB (GPNMB) and pretreated breast cancer. (
  • Current Computer-Aided Drug Design aims to publish all the latest developments in drug design based on computational techniques. (
  • A journal like Current Computer-Aided Drug Design (CC-ADD), which reports on timely comprehensive in-depth reviews and critical assessment of novel directions in the area of drug design and drug discovery, has been long overdue. (
  • Current Computer-Aided Drug Design was introduced in 2005 and Dr. Subhash C. Basak is acting as an Editor-in-Chief since 2012. (
  • Explains the experimental and theoretical methods used to characterize interactions between ligands and receptors-providing the pharmacological information needed to solve treatment problems and facilitate the drug design process! (
  • Loss of the fast-degrading PAA componentenhanced the porosity and hydration of the slow-degrading PTMC.A statistical full factorial model was designed to elucidatethe influence of matrix parameters and their interactions. (
  • The rapid progress in understanding macromolecular (e.g., protein/ligand) interactions at the atomic level of detail makes it possible to design ligands and inhibitors with desired specficities. (
  • This track in part focuses on biophysical concepts, algorithms and software tools aimed at quantitative understanding and predicting protein-ligand interactions, applicable to drug discovery efforts. (
  • Although design techniques for prediction of binding affinity are reasonably successful, there are many other properties, such as bioavailability, metabolic half-life, side effects, etc., that first must be optimized before a ligand can become a safe and efficacious drug. (
  • Whereas ligand-binding design enables the binding of either the antibiotic doxycycline or the anticancer compound doxorubicin, the reengineering of an existing allosteric coupling mechanism enables the release of the bound ligands on occurrence of a proteinase trigger signal. (
  • identifying whether the bound conformation of protein-ligand structure gives the lowest energy state and the impact of drug design. (
  • Analysis and prediction of protein-ligand complexes: database searching, docking, and design. (
  • So ligand-based drug design - it's important to understand what we do and how we achieve it. (
  • There are numerous excellent reviews on fragment-based drug discovery (FBDD), but there are to date no hand-holding guides or protocols with which one can embark on this orthogonal approach to complement traditional high throughput screening methodologies. (
  • Nowadays, in silico methodologies have become a crucial part of the drug discovery process. (
  • The key obstacle for drug delivery in osteoarthritis is the hostile pharmacokinetics of the joint. (
  • Comprehensive and up-to-date, Peptide-Based Drug Design: Methods and Protocols shows its subject to be an independent science on the rise, and provides scientists with a clear, concise guide for continuing this vital research. (
  • In Drug Design and Discovery: Methods and Protocols , leading experts provide an in-depth view of key protocols that are commonly used in drug discovery laboratories. (
  • These tools can help the scientists to shorten the cycle of drug discovery, and thus make the process more cost-affordable. (
  • The book series is essential reading to all scientists involved in drug design and discovery who wish to keep abreast of rapid and important developments in the field. (
  • 2005. Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors: new disease-modifying agents for Alzheimer's disease . (
  • This is a review of the structure and function of biological membranes and other cellular barriers used in drug transport. (
  • Online gamers have solved a longstanding scientific problem, perhaps leading the way to new anti-viral drugs,' said Carter Kimsey, program director in the National Science Foundation's (NSF) Division of Biological Infrastructure, which funded the research. (
  • As a result, designing a new drug is like crafting a three-dimensional jigsaw puzzle piece that fits precisely into an existing biological structure in the body. (
  • Aromatic and benzylic amines add properties to the drug that help it bind more efficiently to these biological structures. (
  • The group, led by professor of chemistry and biochemistry Stewart Schneller, has designed a compound aimed at reversing the immune-blocking abilities of certain viruses, including Ebola. (
  • J. Yang, "Application of Computer-Aided Drug Design to Traditional Chinese Medicine," International Journal of Organic Chemistry , Vol. 3 No. 1A, 2013, pp. 1-16. (
  • Dr. Subhash C. Basak, a Senior Scientist and Adjunct Professor at the University of Minnesota Duluth, has more than 40 years of experience in mathematical /computational chemistry and computer aided drug design. (
  • Frontiers in Drug Design and Discovery is a book series devoted to publishing the latest and the most important advances in drug design and discovery. (
  • The volume delves into contemporary, cutting-edge subjects such as hit isolation and target validation, computer-aided design, sequence modifications to satisfy pharmacologists, in vivo stability and imaging, and the actual production of difficult sequences. (
  • Nevertheless, current drug design also takes into consideration other relevant processes than influence drug efficacy and safety (e.g., bioavailability, metabolic stability, interaction with antitargets). (
  • Furthermore, their unique structures and high stability make them appealing as peptide-based templates for drug design applications. (
  • Designed for stability, the innovative new polymer degrades slowly in the body, giving it more time to work. (
  • The article focuses on the importance of maleimide in improving the stability of antibody-drug conjugates (ADCs) for the treatment of cancer. (
  • In retrometabolic drug design, metabolic reaction information of drugs is used to design parent drugs whose metabolism and distribution can be controlled to target and eliminate the drug to increase efficacy and minimize undesirable side effects. (
  • Uniquely comprehensive, the book relates physicochemistry and chemical structure to pharmacokinetic properties and ultimately drug efficacy and safety. (
  • There's still a lot of work that needs to be done to demonstrate the safety and efficacy of this drug combination before human clinical trials can begin," said Patterson. (
  • Initially, drug-eluting stents (DES) were compared to bare-metal stents (BMS) for efficacy. (
  • Even approved drugs in this category, such as corticosteroids and hyaluronic acid suspensions, are subject to debate with respect to their safety and/or efficacy (3-5) . (
  • This finding is a big step in demonstrating this treatment could be taken as a pill, similar to other HIV drugs, and is suitable for eventual clinical translation. (
  • The authors therefore suggest that glucocorticoid drugs designed to selectively target the glucocorticoid receptor and not LXR-beta should be safer than those currently in clinical use. (
  • Several polymer drug carriers are in clinical trials in the United States and one is already used in Japan. (
  • You would use this information to design and select your carrier, and then you would want to go into clinical trials and see if it works," he says. (
  • Underlying the clinical failures of disease-modifying drugs and the shortcomings of approved drugs is inadequate drug delivery to target joint tissues (6, 7) . (
  • This article provides an overview of some of the design strategies used in drug delivery systems for joints, and discusses important considerations and challenges for clinical translation of these technologies. (
  • The new drug, by contrast, takes effect quickly and lasts at least 30 days, according to clinical studies. (
  • Dr. Samantha Meltzer-Brody , a psychiatrist at the University of North Carolina who led the clinical trials for the drug, said the medication is such an improvement over current therapies that she doubts the IV administration will discourage its use. (
  • Furthermore, there are particular problems in rare diseases and small biomarker defined subsets in oncology, where the required sample sizes for traditional clinical trial designs may not be feasible. (
  • Antibody-drug conjugates are powerful new treatment options for lymphomas and solid tumours, and immunomodulatory antibodies have also recently achieved remarkable clinical success. (
  • After participating in a clinical trial for a new drug designed to prevent migraines, she says she now has only occasional headaches. (
  • In clinical trials, people taking the new drugs reported no more side effects than those taking a placebo. (
  • Dr. Tepper and Dr. Starling, like most leading migraine specialists, have consulted with the drug companies and enrolled patients in their clinical trials. (
  • For a draft review of migraine drug s, the nonprofit Institute for Clinical and Economic Review surveyed patients with frequent migraines. (
  • Dr. Hershey is involved in a clinical trial testing one of the new drugs in 12- to 17-year-olds and plans eventually to enroll children as young as age 6. (
  • If the company's drug candidate proves out during clinical trials, it would be a major step forward both for these patients and the industry as a whole. (
  • SMi presents the 15th Annual Advances and Progress in Drug Design 2016, with a strong focus on advanced biophysical technologies and combinatorial methods enabling greater insight of biologics and drug interaction. (
  • Bielecka AM, Obuchowicz E (2016) Antidepressant drugs can modify cytotoxic action of temozolomide. (
  • He joined Pfizer in 1999, where he is currently a Research Fellow in the Drug Metabolism Group (Groton Laboratories). (
  • In its most common form, it involves modification of a known active scaffold or linking known active scaffolds, although de novo drug design (i.e., from scratch) is also possible. (
  • Hartenfeller M, Schneider G (2011) De novo drug design. (
  • Novo follows Pfizer Inc., AstraZeneca plc and Novartis AG in adopting AI-guided drug design, with the goal of improving efficiency. (
  • Based on its pilot, Novo thinks it can cut in half the time and cost of drug discovery and lead optimization. (
  • Our internationally renowned speakers will also discuss the latest developments in drug design, including anti-target modelling, advances in polypharmacology and structure based design. (
  • Indeed, there has already been considerable improvement in increasing drug potency and specificity, with huge commercial impact world-wide. (
  • Since its introduction by Nicholas Bodor in the late 1970s, the soft drug concept generated considerable research both in academic and in industrial settings. (
  • A dvances in biomedical and pharmacological research have continued to benefit humanity by producing drugs that either alleviate symptoms of disease or provide a cure. (
  • This reference book provides invaluable practical information to the scientist working in drug design or NMR research. (
  • Chilkoti describes their research as "an engineering test to figure out approximate design rules for how you might want to design or select polymers for cancer drug delivery. (
  • AUBURN UNIVERSITY-An Auburn University research team has produced a new drug candidate that could one day slow or even stop the deadly Ebola virus. (
  • The drug design research taking place in his laboratory has focused on combatting a variety of virus-caused infections, including Smallpox, Yellow Fever, Hepatitis C and others. (
  • He has an extensive track record of research, publications and presentations in the area of multi-target drug discovery (MTDD). (
  • Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. (
  • Innovative drug research is of great significance and bright prospects. (
  • This paper mainly discusses CADD and their application to drug research, especially TCM modernization. (
  • These devices are becoming more and more common in research centers, clinics, and hospitals, and are contributing to more accurate studies and therapies, making them a staple technology for future drug design. (
  • The AMR IRG is a unique translational research and entrepreneurship program that aims to solve the growing threat of resistance to antimicrobial drugs. (
  • The Center for Drug Discovery, Design and Delivery (CD4) at Southern Methodist University's Dedman College of the Humanities and Sciences is a novel multi-disciplinary focus for scientific research targeting medically important problems in human health. (
  • Biogen 's plans to resurrect its failed Alzheimer's drug sent shockwaves through the research community, including at local companies. (
  • Design and synthesis of novel graphene-based drug delivery systems. (
  • Chemotherapy drugs wash in and out of tumors quickly and end up attacking healthy tissues. (
  • Tashima T (2015) Possibilities of Cancer Chemotherapy Based on Transporter-Conscious Drug Design. (
  • This type of targeting could reduce side effects, such as when chemotherapy drugs destroy healthy cells instead of cancerous ones, but the biomechanics of this binding process are complex. (
  • Finally, drug design that relies on the knowledge of the three-dimensional structure of the biomolecular target is known as structure-based drug design. (
  • Carlomagno went on to describe a methodology the team have recently developed to support structure-based drug design. (
  • Recent progress in structure-based anti-influenza drug design. (
  • In this review, we present an overview of recent progress in structure-based anti-influenza drug design, paying close attention to the increasing role of computation and strategies for overcoming drug resistance. (
  • The track provides a forum for contributions covering the above, and other relevant aspects of structure-based drug discovery as well. (
  • So structure-based drug design, what is it we're trying to achieve? (
  • Then I'm going to move on to virtual library design where we can enumerate virtual libraries and make predictions about those libraries that can then be tested using structure-based methods. (
  • Each volume is devoted to the major advances in drug design and discovery. (
  • Insilico fits strongly with our strategy of investing in the best-in-class innovators in the healthcare," said Fred Hassan of Warburg Pincus, "Artificial Intelligence and Machine Learning is a powerful tool to revolutionize the drug discovery process and bring life-changing therapies to patients faster than ever before, he added. (
  • This initial screening gave Numerate a head start in the search for possible drugs for Huntington's disease, Griffin says. (
  • and the effects of physical-chemical and ADMET properties of the designed potential drugs. (