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 2.1.1.45.
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.
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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...
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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 find-more-books.com 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=http://www.craigak.com/plan/specification16/form4/]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 https://chidb.com/register/2011/sbd/reg.asp 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...
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 ...
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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 ...
Dear Colleagues,. The 7th Brazilian Symposium on Medicinal Chemistry (BrazMedChem2014) is going to be held at the Campos do Jordao Convention Center, in Campos do Jordao (Sao Paulo State) Brazil, from November 9 to 12, 2014.. In this edition, we envisage to keep the high scientific level that was achieved in previous editions. To accomplish with that, Brazilian and foreign scientists will get together in Campos do Jordao to discuss about the intricacies of the drug discovery process.. The running title of this edition Facing the Turning Point in Medicinal Chemistry was chosen due to the dramatic changes perceived in discovery and development of new bioactive molecules. The role of the medicinal chemist is under revision with a reposition as a response to this scenario, once medicinal chemistry plays a critical role in this area.. This event also wants to contribute to the education of undergrad and graduate students in the medicinal chemistry field, once they correspond to the majority of the ...
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 ...
The first is referred to as ligand-based drug design and the second, structure-based drug design. Ligand-based drug design (or ... Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new ... The phrase "drug design" is to some extent a misnomer. A more accurate term is ligand design (i.e., design of a molecule that ... Structure-based drug design (or direct drug design) relies on knowledge of the three dimensional structure of the biological ...
In retrometabolic drug design, metabolic reaction information of drugs is used to design parent drugs whose metabolism and ... In the field of drug discovery, retrometabolic drug design is a strategy for the design of safer drugs either using predictable ... Soft drugs and site-specific chemical delivery systems". Adv. Drug Res. 13: 255-331. Retrometabolism-based drug design and ... The concept of retrometabolic drug design encompasses two distinct approaches. One approach is the design of soft drugs (SDs), ...
... is a peer-reviewed medical journal covering research on drug design and development ...
The drag coefficient is a common measure in automotive design as it pertains to aerodynamics. Drag is a force that acts ... A common way to measure the drag of the vehicle is through the drag area. The reduction of drag in road vehicles has led to ... The two main factors that impact drag are the frontal area of the vehicle and the drag coefficient. The drag coefficient is a ... The force F required to overcome drag is calculated with the drag equation: F = 1 2 × air density × drag coefficient × ...
... s or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. ... Beck A, Goetsch L, Dumontet C, Corvaïa N (March 2020). "Advances in Antibody-Drug Conjugate Design: Current Clinical Landscape ... "Ambrx Collaborates with Merck to Design and Develop Biologic Drug Conjugates". Archived from the original (Press Release) on ... "Approved Drugs > FDA Approves Gemtuzumab Ozogamicin for CD33-positive AML". fda.gov. Silver Spring, USA: U.S. Food and Drug ...
Boppe, C. W., "CFD Drag Prediction for Aerodynamic Design", Technical Status Review on Drag Prediction and Analysis from ... is the drag-divergence Mach number, c l , design {\displaystyle c_{l,{\text{design}}}} is the coefficient of lift of a specific ... have been able to reduce the factor of increase in drag to two or three for modern aircraft designs. Drag-divergence Mach ... The drag-divergence Mach number (not to be confused with critical Mach number) is the Mach number at which the aerodynamic drag ...
Drug Design, Development and Therapy. 15: 2921-2945. doi:10.2147/DDDT.S295224. PMC 8273751. PMID 34262259. S2CID 235820469. " ... A disease-modifying osteoarthritis drug (DMOAD) is a disease-modifying drug that would inhibit or even reverse the progression ... anti-diabetic drug: NCT04767841, NCT05034029), Zoledronic acid (anti-osteoporotic drug: NCT04303026), and etc. Paroxetine has ... Several approved drugs are being investigated as repurposed agents in the treatment of osteoarhritis such as liraglutide (anti- ...
"New spiral molecular drag stage design for high compression ratio, compact turbomolecular-drag pumps". Journal of Vacuum ... While the molecular drag pumps of Gaede, Holweck, and Siegbahn are functional designs, they have remained relatively uncommon ... A molecular drag pump is a type of vacuum pump that utilizes the drag of air molecules against a rotating surface. The most ... A. Bhatti, J; K. Aijazi, M; Q. Khan, A (2001). "Design characteristics of molecular drag pumps". Vacuum. Elsevier BV. 60 (1-2 ...
Another method for drug discovery is de novo drug design, in which a prediction is made of the sorts of chemicals that might (e ... "The drug development process. Step 4: FDA drug review". US Food and Drug Administration. 4 January 2018. Retrieved 18 December ... Antitarget Bioinformatics Biomedical informatics Cheminformatics Drug discovery hit to lead Drug metabolism Fragment-based drug ... and pass through a new drug approval process, called the New Drug Application in the United States. Discovering drugs that may ...
Hyneck, M (1990). Chirality in Drug Design and Synthesis. New York: Academic Press, New York. pp. 1-28. Cotzias, George C.; Van ... Hence "chiral drug" does not say whether the drug is racemic (racemic drug), single enantiomer (chiral specific drug) or some ... Drugs that exhibit handedness are referred to as chiral drugs. Chiral drugs that are equimolar (1:1) mixture of enantiomers are ... The table below list selected unichiral drugs used in drug therapy. A company may go in for developing a racemic drug against ...
Hopkins, A; Mason, J; Overington, J (2006). "Can we rationally design promiscuous drugs?". Current Opinion in Structural ... In pharmacology, a dirty drug is an informal term for drugs that may bind to many different molecular targets or receptors in ... There may be instances of advantages to drugs that exhibit multi-receptor activity such as the anti-addictive drug ibogaine ... Selectively non-selective drugs for mood disorders and schizophrenia". Nature Reviews Drug Discovery. 3 (4): 353-9. doi:10.1038 ...
Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9780120603084. Ojasoo T, Delettré J, Mornon JP, Turpin- ... Drugs missing an ATC code, Drugs with no legal status, Articles containing unverified chemical infoboxes, Tertiary alcohols, ... Unlisted Drugs. Pharmaceutical Section, Special Libraries Association. 1982. Batynid. C. Each dragee contains: normethandrone, ... 898-. ISBN 978-1-4757-2085-3. Drugs.com. "Methylestradiol". Retrieved 2 January 2016. IARC Working Group on the Evaluation of ...
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 ... Drugs with no legal status, Abandoned drugs, Tertiary alcohols, Ethynyl compounds, Androgens and anabolic steroids, Estranes, ... 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 ...
... drug design; nanoparticle structure and energetics; and density functional theory, including the Minnesota Functionals. To date ...
Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9780120603084. Ojasoo T, Raynaud JP (November 1978). " ...
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. Vol. 25. pp. 478-502. doi:10.1016/S0378-6080(02)80047-2. ISBN 9780444506740. ISSN 0378-6080. ... 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.{{cite journal}}: CS1 maint: untitled periodical (link) Martin-Smith M (1971), In: Ariens EJ (ed.), "Drug Design ... Drugs with no legal status, Drugboxes which contain changes to verified fields, Allyl compounds, Muscle relaxants, ... 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 (Articles without EBI source, ... It is a potent antagonist of the mineralocorticoid receptor and is more potent than the related drug SC-5233 (of which SC-8109 ... Drugs with no legal status, Articles containing unverified chemical infoboxes, Antimineralocorticoids, Diuretics, Lactones, ... Chemical pages without DrugBank identifier, Articles without KEGG source, Articles without UNII source, Drugs missing an ATC ...
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, ... Drugs missing an ATC code, Drugs with no legal status, Articles containing unverified chemical infoboxes, Abandoned drugs, ... Secondary alcohols, Estranes, Human drug metabolites, Synthetic estrogens, All stub articles, Genito-urinary system drug stubs ...
... 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 ... such as poor-quality drugs. In the region, research spending has hovered around the 0.2-0.3% mark for the past decade but, in ...
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 ... 61-. ISBN 978-1-4831-5308-7. (Drugs with non-standard legal status, Chemical pages without DrugBank identifier, Articles ...
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 ... Drugs with no legal status, Abandoned drugs, Secondary alcohols, Androgens and anabolic steroids, Antigonadotropins, ... It is also commonly known as 7α-methyl-19-nortestosterone (MENT). J. Elks (14 November 2014). The Dictionary of Drugs: Chemical ... CS1 Chinese-language sources (zh), Articles with short description, Short description matches Wikidata, Drugs not assigned an ...
Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9780120603084. Kohtz, Amy S.; Frye, Cheryl A. (2012). " ... Drugs with no legal status, Articles containing unverified chemical infoboxes, Abandoned drugs, Tertiary alcohols, Estranes, ... 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 ...
Drug Design. pp. 169-214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9780120603084. Ojasoo T, Raynaud JP (November 1978). " ... Drugs missing an ATC code, Drugs with no legal status, Articles containing unverified chemical infoboxes, Anti-acne ... The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 899-. ISBN 978-1-4757-2085- ...
Retrometabolic drug design Neuroscience, Purves et al. Sinauer Associates, Inc. 2008. Rubin, L. L., & Staddon, J. M. (1999). ... Drugs can be disguised using more lipophilic elements or structures. This form of the drug will be inactive because of the ... The most promising drug delivery system is using nanoparticle delivery systems, these are systems where the drug is bound to a ... Once the drug cannot pass back through the barrier the drug can be concentrated and made effective for therapeutic use. However ...
Rational drug design. Boca Raton: CRC Press. ISBN 0-8493-7818-4. {{cite book}}: ,first1= has generic name (help) Ganten, edited ... Zwieten, edited by Pieter A. van; Greenlee, William J. (1997). Antihypertensive drugs. Amsterdam, the Netherlands: Harwood ...
... 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 ...
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 ...
Womp drugs Steve and attempts to smother him, but just can't do it. Meanwhile, Steve has a flashback: years ago, when Steve was ... Steve decides that comfort is the root of all weakness, so he designs a collection of fistworthy furniture (which offers pain ... such that it can be dragged towards an operating lawn-mower. Steve asks the teams numerical questions, and the amount by which ...
The Prince P.16 was a radical design by Captain A.G. Forsyth who was the Fairey company's chief engine designer. The Prince was ... and the drag of both engine nacelles can be eliminated and combined within the cross-section of the fuselage. Fairey Battle P. ... The Fairey P.16 Prince was a British experimental 1,500 hp (1,118 kW) 16-cylinder H-type aircraft engine designed and built by ... Unfortunately, a conventional twin could not be designed so that it came within the size limits for aircraft carrier use on the ...
... were designed by effects assistant Mike Trim in his first major design work for APF. In the series' alternative two-part format ... Brains predicts that if the rest of the top-soil crust over the pit is removed, the Recovery Vehicles will be able to drag the ... The Sidewinder's look was designed by director Desmond Saunders. The studio model used wood and card for the main body and ... Continuity errors in the design of the army helicopter cockpit set distinguish the episode's original footage from the new ...
The AIA Guide to the Architecture of Washington, D.C. summed up the design: "For all its quirks, the awkward tower reigns as ... The Cairo began to decline during the 1960s, when it was inhabited by squatters, prostitutes, drug addicts, student protesters ... Designed by architect Thomas Franklin Schneider and completed in 1894 as the city's first "residential skyscraper", the 164- ...
... monophosphate decarboxylase support a covalent mechanism and provide a framework for drug design". Structure. 16 (1): 82-92. ...
Design defects Claims of design defects allege that tobacco companies designed tobacco products with additional adverse health ... March 2001: The US Supreme Court affirmed the Circuit Court's ruling that the Food and Drug Administration could not class ... Examples of design defects include cigarettes that increase addiction risks and deliberately choosing to not develop less ... but instead carefully and thoughtfully design the least hazardous tobacco product for smokers. Strict liability Under a theory ...
They believed their sons were targeted for inappropriate drug test procedures and inappropriate action taken after drug tests ... The facility is designed to accommodate 104 students which represents over 10 percent of the school roll. The Ministry of ... "Drugs; whether use of, in possession of, or supply of, will not be tolerated or accepted." Mr Finn told The Daily Post he held ... Taipari, Greg (2 July 2010). "Mother wants 'heads to roll' over drug probe". Rotorua Daily Post. "The pain behind Israel ...
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. The term autism encompasses a wide range of syndromes, such as Rett disorder, ...
Selection Versus Design in Chemical Engineering The ETH-2 human antibody phage library Sidhu SS, Lowman HB, Cunningham BC, ... Lawrence S (April 2007). "Billion dollar babies--biotech drugs as blockbusters". Nat. Biotechnol. 25 (4): 380-2. doi:10.1038/ ... To overcome the size problem of pVIII, artificial coat proteins have been designed. An example is Weiss and Sidhu's inverted ... Weiss GA, Sidhu SS (June 2000). "Design and evolution of artificial M13 coat proteins". J. Mol. Biol. 300 (1): 213-9. doi: ...
An example of a source of this uncertainty would be the drag in an experiment designed to measure the acceleration of gravity ... For example, the dimensions of a work piece in a process of manufacture may not be exactly as designed and instructed, which ... The probabilistic approach is considered as the most rigorous approach to uncertainty analysis in engineering design due to its ... On the other hand, the latter problem is drawing increasing attention in the engineering design community, since uncertainty ...
The drag produced having the landing gear stowed in the up position is higher than in the extended position, and this reduces ... The Teal design features a high wing with tip floats for lateral stability. The horizontally opposed engine is mounted tractor ... The aircraft was designed to be very rugged and simple, with manually operated flaps and landing gear. The conventional ( ... The Thurston Teal is a family of two- and four-seat all-aluminium amphibious aircraft designed by David Thurston in the United ...
It is the only drug store in the city owned and operated by colored people and it is a real credit to Lynchburg." In 1936, Reid ... created two design options for an upgrade and expansion of the building. The first option involved reconfiguring the left ... Drug stores, cafes, barbershops, pool halls, grocery and clothing stores, news-stands and theaters…are operated for Negroes by ... Designed by Lynchburg architects Samuel Preston Craighill and Bennett Cardwell in 1919, the one-story building features the ...
The design that was produced was not acted upon by Congress, and the Great Seal's design was not finalized until a third ... Merchants in all thy ports are encouraged by thy laws to continue a commerce whereby so many hundreds of thousands are dragged ... "1782: Original Design of the Great Seal of the United States", Our Documents: 100 Milestone Documents from the National ... On July 4, 1776, Congress appointed a three-member committee composed of Franklin, Jefferson, and Adams to design the Great ...
The 1985 maximum power allowed by the U.S. Food and Drug Administration (FDA) of 180 milliwatts per square cm is well under the ... This was the start of the most popular design in the history of ultrasound scanners. Obstetric ultrasound has played a ... "Fetal Keepsake Videos". Food and Drug Administration. Retrieved 2011-05-21. "Statement on Measurement of the Fetal Heart Rate ...
After three years, there were major documented reductions in crime, drug dealing, teenage pregnancy, child abuse, child neglect ... however weak or strong the design, has shown decreases in problem behaviors and internally experienced problems. This approach ... County of Santa Clara Department of Alcohol & Drug Services Health Realization Services Division, 2007. Retrieved Oct. 19, 2007 ... drugs, or other compulsive behaviors in the attempt to quell their stressful feelings and regain some momentary sense of ...
The tower did use a design of the United States flag during the July 4 holidays, as well as the American hostage crisis of 1980 ... Also headquartered in El Paso are the Drug Enforcement Administration domestic field division 7, El Paso Intelligence Center, ... During the Christmas holidays, a design of a Christmas tree was used, and at times, the letters "UTEP" were used to support ... the only public premium daily fee Tom Fazio designed golf course in the state of Texas. It was ranked No. 1 in Texas and No. 3 ...
Lundborg M, Ali E, Widmalm G (2013). "An in silico virtual screening study for the design of norovirus inhibitors: fragment- ... Ali ES, Rajapaksha H, Jillian MC, Petrovsky N (2016). "Norovirus drug candidates that inhibit viral capsid attachment to human ... by reverse transcription polymerase chain reaction are being employed by governmental laboratories such as the Food and Drug ...
The design of the rear is also different, with new eyelid-like fixed flaps that continue with the design and eventually end on ... All of the exterior components in the car are used to optimize downforce and drag. The Huayra BC uses an Xtrac 7-speed ... The design of the car reflects Horacio's visit with each unit's livery design resembling one of the dragons on the wall, and it ... Air from the radiator is extracted through an arch in the bonnet at an angle that is designed not to affect the streamline ...
The PLATO system was re-designed, between 1963 and 1969; PLATO III allowed "anyone" to design new lesson modules using their ... and Bugs-n-Drugs (a medical variation)-all presaging MUDs (Multi-User Domains) and MOOs (MUDs, Object Oriented) as well as ... Although PLATO was designed for computer-based education, perhaps its most enduring legacy is its place in the origins of ... PLATO was designed and built by the University of Illinois and functioned for four decades, offering coursework (elementary ...
Based on the design of the Alstom Coradia Juniper family, early plans for some of the fleet to be ran at 125 mph (200 km/h) ... Its launch operator stated that the train possessed both reduced drag and improved fuel efficiency over its existing rolling ... The exterior of the Class 175 has been designed for improved aerodynamics over preceding rolling stock; it is equipped with a ... The interiors were built to a bespoke design specified by the initial operator, North Western Trains. Various amenities are ...
... production without retail sale by the European Monitoring Centre for Drugs and Drug Addiction What is a Cannabis Social Club by ... Decorte, Tom; Pardal, Mafalda (2020), "Insights for the design of Cannabis Social Club regulation", Legalizing Cannabis, pp. ... European Monitoring Centre on Drugs and Drug Addiction, 05.31.2016, Models for the legal supply of cannabis: recent ... Legality of cannabis Drug policy Cannabis shop San Francisco Cannabis Buyers Club ENCOD Allotment (gardening); quite similar ...
Designer Marc Friedland designed a new envelope heralding the winner of each category made from a high-gloss iridescent ... "These Oscars were a bore-fest that seemed to drag on relentlessly but listlessly." Gail Pennington of the St. Louis Post- ... King, Susan (February 16, 2011). "Oscars: The envelope gets a new design". Los Angeles Times. Archived from the original on ... Production designer Steve Bass built a new stage design for the ceremony. Entertainment Weekly columnist and TV personality ...
"Aerospace Design Lab: Noël Bakhtian". adl.stanford.edu. Retrieved 2018-09-08. "Stanford ESP - Noel Bakhtian". stanfordesp.org. ... Bakhtian explored using such thrusters to change the shape of the leading bow shock so as to increase the decelerative drag ... She completed her thesis, Drag Augmentation via Supersonic Retropropulsion for Atmospheric Deceleration, in 2012. Whilst a ...
Also in 1913, Hughes published his book Dress Design: an account of costume for artists and dress makers, illustrated by the ... and the unwilling drags" (1900) and "The Road of Love" (1900). Talbot Hughes amassed a collection of over 750 historical ... and a writer on fine art and costume design. He exhibited at the Royal Academy from the age of 17 until 1913. Talbot Hughes was ... Dress Design: an account of costume for artists & dressmakers, Pitmann & Sons, 1920 Old English Costumes More Clothing Examples ...
... but not Don Henley-were also unhappy with the no-drug policy of Johns during the recording; furthermore they did not feel at ... design Ruhlmann, William. "Eagles - On the Border". AllMusic. All Media Network. Retrieved August 27, 2014. Richard Buskin ( ... who had died of a drug overdose in September 1973. Leadon and Parsons had been members of the pioneering country-rock band The ...
The music had become "too hard, too fast, too male, too drug-oriented, too anally retentive." Despite this, weekly night at ... but the design of synthetic timbres, and the creative use of music production technology in general, are important aspects of ... as a party drug, started to gain prominence. Other important UK clubs at this time included Back to Basics in Leeds, ... and musical design in electronic dance music. Bloomington: Indiana University Press, page 78. "...Drawing on two of the most ...
The website was updated after protests and now holds that no such risk has been found in recent, well-designed studies. The ... The United States Department of the Interior, the National Oceanic and Atmospheric Administration, and the Food and Drug ... The intelligent design movement associated with the Discovery Institute, attempts to "defeat [the] materialist world view" ... cited in Handley P. Evolution or design debate heats up. The Times of Oman, 7 March 2005. National Academy of Science Institute ...
Designing an adequate diffuser for a rebreather is much easier than for open-circuit scuba, as the gas flow rate is generally ... An excess of tubes and connections passing through the water tend to decrease swimming performance by causing hydrodynamic drag ... of Florida co-designed such a scuba in 1967, called "Mako", and made at least five prototypes. The Russian Kriolang (from Greek ... The amount of gas lost from the circuit during each breathing cycle depends on the design of the rebreather and depth change ...
They say it is designed to facilitate, but not replace, that process. Raters 'have every right to change [the symptoms] if ... "was a result of his or her abuse of alcohol or drugs". In order for a veteran to receive disability benefits for PTSD, the ... The CAPS is a structured clinical interview designed to assess symptoms of PTSD corresponding to DSM-IV criteria. The CAPS has ... DBQs replace traditional VA examination reports and are designed to capture all the needed medical information relevant to a ...
The fuselage of the Buccaneer was designed using the area rule technique, which had the effect of reducing aerodynamic drag ... The Blackburn Buccaneer is a British carrier-capable attack aircraft designed in the 1950s for the Royal Navy (RN). Designed ... Blackburn proposed two designs, the B.103A, a simple modification of the Buccaneer S.1 with more fuel, and the B.108, a more ... However, design changes for the Mark 2 Buccaneer, the addition of extended wingtips and the position of a new bolt hole, did ...
Soteras, I, Curutchet C, Bidon-Chanal A, Dehez F, Angyan JG, Orozco M, Chipot C, Luque FJ. 2007. Derivation of distributed models of atomic polarizability for molecular Simulations. Journal of Chemical Theory and Computation. 3(6):1901-1913. Abstract ...
... medicinal chemists are now ready to embrace AI-based methods and concepts in drug discovery, explains Gisbert Schneider. ... Mind and machine in drug design. *Gisbert Schneider. 1 Nature Machine Intelligence volume 1, pages 128-130 (2019)Cite this ... 1: Cartoon representation of the drug design cycle as the interplay of inductive and deductive reasoning.. Jack Burgess. ... successful drug repurposing, improved accuracy for drug property predictions, and the autonomous generation of drug candidates ...
Brough, PA, Aherne W, Barril X, Borgognoni J, Boxall K, Cansfield JE, Cheung KM, Collins I, Davies NG, Drysdale MJ et al.. 2008. 4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer. Journal of medicinal chemistry. 51(2):196-218. Abstract ...
Combination with synthesis planning and ease of synthesis is feasible and more and more automated drug discovery by computers ... Artificial intelligence in de novo design drives the generation of meaningful new biologically active molecules towards desired ... plays a pivotal role in drug discovery. In particular artificial neural networks such as deep neural networks or recurrent ... Jing, Y.; Bian, Y.; Hu, Z.; Wang, L.; Xie, X.S. Deep Learning for Drug Design: An Artificial Intelligence Paradigm for Drug ...
The seizure drug is meant to be customized for high dosage treatments, and was developed with Aprecias ZipDose technology. ... The use of 3D-printing for medical purposes is not new, but this is the first time the FDA has approved a drug designed by 3D- ... The FDA has approved the first drug designed using 3D-printing technology August 4, 2015 - 12:21 am. ... SPRITAMs 3D-printed designed makes it water soluble with a minimal amount of liquid, which absorbs into the blood stream in ...
Rethinking how we design drugs. Two details in A2aARs structure gave researchers insight into how future drugs could ... Scientists at The Scripps Research Institute (TSRI) have peered deep into the heart of a key protein used in drug design and ... "This basic knowledge is potentially helpful for improving drug design," says Nobel laureate Kurt Wüthrich, PhD, the Cecil H. ... "But for a long time, drug design was being done without knowing how GPCRs looked." ...
... and MIT have developed nanometer-sized hybrid structures carrying anti-cancer drugs and quantum dot imaging agents. ... View MoreAnalytical Method DevelopmentAPIsAseptic ProcessingBiologic DrugsDrug DeliveryEquipmentExcipientsFormulationPackaging ... Analytical Method DevelopmentAPIsAseptic ProcessingBiologic DrugsDrug DeliveryEquipmentExcipientsFormulationPackagingProcess ... The protein F3, designed to adhere to cancer cells and transport into the cells nuclei, is tethered to the surface of the ...
... often called computer-aided drug design - refers to the drug invention process that relies on computer modeling. ... Computational drug design - often called computer-aided drug design - refers to the drug invention process that relies on ... What is Computational Drug Design?. Drug design is the process of finding and testing new treatments based on biological ... Computational drug design has been significantly improved by advances in algorithms, large amounts of data and improved ...
Taking advantage of the physiological signals, redox-responsive polymeric drug carriers cons ... Redox-responsive polymers for drug delivery: from molecular design to applications Meng Huo,ab Jinying Yuan,*a Lei Taob and Yen ... Redox-responsive polymers for drug delivery: from molecular design to applications M. Huo, J. Yuan, L. Tao and Y. Wei, Polym. ... In this review, we discuss the reduction- and oxidation-responsive polymeric drug carriers from the view of functional groups, ...
... have been widely used for drug design and drug discovery. To design successful drugs, it takes collaborative efforts from ... Some of the most fruitful approaches in the field are computer-aided drug design and drug-delivery design that offer the ... Rational drug design and drug discovery have rapidly evolved into some of the most important and exciting research fields in ... protein-based drugs, mRNA-based and CRISPR-based drugs have become increasingly common recently. A successful drug must be non- ...
EPFL scientists have created a new computer model that can help better design of allosteric drugs, which control proteins at a ... The main reason allosteric sites are of such interest to drug design is that they can be used to inhibit or improve the ... EPFL scientists develop new computer model for better design of allosteric drugs. *Download PDF Copy ... Because of this, one of the biggest efforts in drug design today aims to control enzymes without interfering with their so- ...
Employers take lead drug benefit design. April 14, 2021. by Paul Lendner ... Drug-Gene Interactions: Inherent Variability in Drug Maintenance Dose Requirements. Schizophrenia: Overview and Treatment ... World Orphan Drug Congress Europe 2014. Brussels, Belgium. November 12-14, 2014. ... without having to design each offering for a self-insured companys likes and dislikes. "In our model theres more control and ...
I have a Hondo flat bottom drag boat that i... ... Boat Design Directory. * Boat Design Gallery Boat Design ... Home Boat Design Forums , Construction , Boatbuilding , Core and Stringer replacement - Hondo Drag Boat. Discussion in ... Forum software by XenForo™ ©2010-2017 XenForo Ltd. Web Site Design and Content Copyright ©1999-2023 Boat Design Net ... Boat Design Net does not necessarily endorse nor share the view of each individual post.. When making potentially dangerous or ...
Adaptive trial designs are also increasingly discussed. However, adaptive should not be used as euphemism for the repurposing ... Adaptive trial designs are also increasingly discussed. However, adaptive should not be used as euphemism for the repurposing ... Adaptive licensing can be a counter-part of adaptive trial design. The use of Big Data is another opportunity to leverage ... Adaptive licensing can be a counter-part of adaptive trial design. The use of Big Data is another opportunity to leverage ...
These results will be used to construct a machine learning framework that will unravel the atomistic origins of drugs ... Machine learning algorithms can predict the solubility of novel drugs without the need of actually synthetizing them - thus ... will address this pitfall by generating three-dimensional molecular models of crystalline drugs polymorphs and simulate their ... The solubility of pharmaceutical drugs determines to what extent they can be absorbed. ...
... demonstrating its potential in speeding the drug discovery process. ... including drug design.. "In drug design, we found that TML provided insight into drug target specificity, the relationships ... better than anything else we know for drug design," said King. "Its better at choosing drugs than humans are -- and without ... outperformed current ML methods in drug design, demonstrating its potential in speeding up the drug discovery process, ...
Drug Design and Development - Explore from the MSD Manuals - Medical Consumer Version. ... Drug administration is the giving of a drug by one of several means (routes). Drug kinetics... read more ) and what the drug ... Many of the drugs Overview of Drugs A drug is defined by U.S. law as any substance (other than a food or device) intended for ... These factors involve what the body does to the drug (drug kinetics Introduction to Administration and Kinetics of Drugs See ...
Product Design. * Top 10 3D-printed designs that every sustainability lover needs to incorporate in their life ... About Yanko Design. Were an online magazine dedicated to covering the best in international product design. We have a passion ... The vision to design this desirable Bugatti is to have a street-legal race car that has the signature Chiron DNA, still being ... This makes one get the feeling that this is a more open Chiron on steroids, ready for any drag race battle on the streets. ...
2022 Drug Plan Trends Report: High-cost drugs, DEI shaping drug plans This month marks the second anniversary of the beginning ... Using proactive drug plan design to ensure future sustainability Ensuring plan sponsors get value for money from their drug ... How PMPRB amendments could impact employers, drug plan design The amendments to the Patented Medicine Prices Review Board ... Coverage of the 2021 Face to Face in Drug Plan Management Forum On Dec. 15, the industrys most popular drug benefits ...
The dominant paradigm that has ruled drug discovery for decades is giving way to a new age of multispecific drugs that harness ... The drug itself does all the hard work of dialing the activity up or down, most often down. Thats drug design in a nutshell. ... A Sea Change in Drug Design. The dominant paradigm that has ruled drug discovery for decades is giving way to a new age of ... Wave 2 introduced rational drug design-specific compounds aimed at specific molecular targets that play a role in disease. Drug ...
Researchers have designed a polymer membrane with molecular cages built into its pores that could allow high-voltage battery ... Designing Selective Membranes for Batteries Using a Drug Discovery Toolbox. April 7, 2021 ... Home » News » News » Science News » Designing Selective Membranes for Batteries Using a Drug Discovery Toolbox ... Scientists at Berkeley Labs Molecular Foundry used a drug-discovery toolbox to design the selective membranes. The technology ...
Here you have a split between people who use drugs and other stakeholders. People who use drugs preferred drug consumption ... More things to consider when designing drug consumption rooms. *A mix of cubicles (for privacy) and open tables to accommodate ... A recent study reviewed key features to consider when designing a drug consumption room. From chill-out rooms to existential ... This study showed that its really important to understand what these needs are when designing, planning and staffing drug ...
Browsing: Drug Study Design. Dog News August 19, 2018 0 FDA Extends Comment Period For Design of Studies for Drugs for ... August 17, 2018 Update: The FDA is extending the comment period for the request for comments on the design of… ...
Nearly three years after Texas enacted a law requiring some applicants for unemployment benefits to pass a drug test, the state ... and then only after they pass a subsequent drug test. Within a week of receiving notice of a failed drug test, an applicant can ... "If youve got a drug problem, there are ways that we can help you get that licked, but were not going to entice individuals to ... "We do have a lot of evidence that a lot of applicants cannot pass a drug test," Hammond said. "Therefore, its likely that some ...
About Yanko Design. Were an online magazine dedicated to covering the best in international product design. We have a passion ... Product Design. * ChaiBot is the worlds first automated tea-brewing machine that perfectly makes tea, chai, and even matcha ... The drag racing theme is spilled onto the rearrangement of the dash which now sits on top of the body kit behind the handlebars ... This Formula 1 car-design bridges the gap between race-cars and fighter-jets Whats the difference between an F1 car and a ...
Design & Optimization for Novel Therapeutics Lab explores variants of unknown significance role in individualized medicine. ... Current Drug Discovery Technologies. 2020; doi:10.2174/1570163817666200311114819.. *Richter JE Jr, Vadlamudi C, Macklin SK, ...
SeeSAR is an interactive and visual molecular modeling and drug design platform for compound evolution and priorization backed ... Everyday drug design dashboard SeeSAR is your intuitive, visual drug design platform. Covering every step of your drug ... SeeSAR is your intuitive, visual drug design platform. Covering every step of your drug discovery process - from virtual ... The seamless integration between StarDrop and SeeSAR provides a state-of-the-art drug design and development platform to our ...
... for design engineers, engineering managers, industry executives, and academia, working on IC, embedded systems and PCB design. ... Tech Design Forum is a curated website about IC, embedded systems and PCB design, ... Food and Drug Administration. July 16, 2021. How to meet formal embedded software guidance for medical devices. Vulnerabilities ... in connected healthcare products have led medical requlators to issue further security recommendations for their design and ...
If readers are unfamiliar with Army Design Methodology, they should refer to U.S. Army Field Manual 5-0, Operations, Chapter 3 ... Cartel NextThis paper is a theoretical exercise that attempts to deliver one possible Army Design solution to the narco- ... or Field Manual 3-24, Counterinsurgency, Chapter 4. Design proposes different systems of logic for making sense of the world ... How Army Design Methodology Offers Holistic and Dissimilar Approaches to the Mexican Drug Problemby Ben ZweibelsonDownload the ...
... a Distribution Facility Design Build Construction Example from Clayco. ... Click here to learn more about Longs Drug Stores Corporation in Patterson, CA, ... Longs Drug Stores Corporation This 800,000-square-foot facility includes 32-foot clear heights and an ESFR sprinkler system.. - ... Clayco completed construction on a distribution facility for Longs Drug Stores Corporation, the latest tenant in a new ...
  • After a difficult start, medicinal chemists are now ready to embrace AI-based methods and concepts in drug discovery, explains Gisbert Schneider. (nature.com)
  • Commercial drug discovery faces a constantly decreasing return on investment. (nature.com)
  • Without question, there is a need for fresh thinking, new and revised conceptions of the drug discovery process, and innovative approaches to deliver higher quality drugs at a lower cost to market. (nature.com)
  • Artificial Intelligence (AI) plays a pivotal role in drug discovery. (mdpi.com)
  • Rational drug design and drug discovery have rapidly evolved into some of the most important and exciting research fields in mathematical medicine and biology, with the potential to have a profound impact on human health. (utoronto.ca)
  • Some of the most fruitful approaches in the field are computer-aided drug design and drug-delivery design that offer the improved understanding of molecular mechanism, dramatically reduced number of experimental drug candidates and efficient strategies for drug discovery. (utoronto.ca)
  • Many mathematical theories, such as differential and algebraic geometry, algebraic topology, graph theory, combinatorics, algebra and differential equations play an integral and essential role in most new developments in computer-aided drug design and discovery. (utoronto.ca)
  • Additionally, mathematical approaches, such as geometric and charge analysis for protein-drug binding site analysis, persistent homology for protein-drug binding detection, manifold learning for discriminating false protein-drug interfaces, and machine learning techniques for high throughput drug screening, have been widely used for drug design and drug discovery. (utoronto.ca)
  • This workshop will bring together experts from both academia and pharmaceutical industry (mathematical and computational scientists, biophysicists, and experimentalists) to develop solutions to challenging problems in drug design and discovery. (utoronto.ca)
  • December 1, 2021 -- A new approach to machine learning (ML) outperformed current ML methods in drug design, demonstrating its potential in speeding up the drug discovery process, according to research published online November 29 in the Proceedings of the National Academy of Sciences . (scienceboard.net)
  • The researchers said that TML shows particular promise in the area of drug discovery. (scienceboard.net)
  • The paper includes a case study using TML to predict quantitative structure activity relationships (QSAR), a common step in early-phase drug discovery. (scienceboard.net)
  • Beginning with the introduction of aspirin at the start of the 20th century, there have been three major waves of innovation in drug discovery. (amgen.com)
  • Scientists at Berkeley Lab's Molecular Foundry used a drug-discovery toolbox to design the selective membranes. (nersc.gov)
  • To pinpoint a design for a cage in a membrane that would solvate lithium ions, Helms and his team looked to a widely practiced drug discovery process. (nersc.gov)
  • In drug discovery, it's common to build and screen large libraries of small molecules with diverse structures to pinpoint one that binds to a biological molecule of interest. (nersc.gov)
  • The use of Big Data is another opportunity to leverage existing information into knowledge useable for drug discovery and development. (frontiersin.org)
  • Covering every step of your drug discovery process - from virtual screening to fragment-based design - SeeSAR fosters ideation in the most fun and comprehensive way. (biosolveit.de)
  • According to Exscientia, designing selective molecules with dual targets continues to be a major challenge for conventional drug discovery, particularly for psychiatric indications which require exceptional selectivity to avoid off-target effects. (europeanpharmaceuticalreview.com)
  • The combination of Exscientia's AI with our company's deep experience in monoamine G-protein coupled receptor (GPCR) drug discovery has now led to two molecules reaching our clinical pipeline from this collaboration. (europeanpharmaceuticalreview.com)
  • This approach is gaining increasing recognition as a valuable tool in drug discovery. (drugdiscoverytoday.com)
  • Application-Based Drug Discovery Workshop: Drug Design. (simulations-plus.com)
  • In silico approaches can drive drug discovery by speeding up the process, improving compound quality, and reducing in vitro/in vivo testing. (simulations-plus.com)
  • The process of drug discovery and drug design is a time-consuming process with the goal of obtaining potent, yet safe and applicable drugs. (meilerlab.org)
  • The process of drug discovery can be aided by computational methods (CADD = computer aided drug discovery), such as quantitive structure activity relation (QSAR) , ligand docking , protein-ligand docking and virtual high-throughput screening . (meilerlab.org)
  • Reporting in the Journal of Medicinal Chemistry (2016, 59, 9, 4087-4102), Dr Martin Stahl and team from Roche Pharmaceutical Research and Early Development discuss use cases and the role of computational methods in molecular design in small molecule drug discovery. (cam.ac.uk)
  • The discovery of small molecule drug candidates is an iterative optimization process, consisting of designing, making, testing, and analysing. (cam.ac.uk)
  • The critical phase is the design phase, where all information on previous rounds of discovery is integrated to decide on the next round of compounds to be synthesised and evaluated. (cam.ac.uk)
  • The case studies demonstrate the power of combining computational query techniques with experimental structural data and qualitative expert assessment in the molecular design phase of drug discovery at Roche. (cam.ac.uk)
  • Mining this data with clever computational methods will continue to create value in drug discovery. (cam.ac.uk)
  • New York, Oct. 20, 2022 (GLOBE NEWSWIRE) - Insilico Medication, a clinical-stage synthetic intelligence (AI)-driven drug discovery firm, is using the identical deepfake know-how used to create art work and lifelike photographs of digital human beings to design new molecules which have the potential to deal with illness. (queenofarticle.com)
  • Conventional drug discovery is gradual, inefficient, and costly. (queenofarticle.com)
  • Insilico is led by a staff of consultants in AI and drug discovery and growth and has a Nobel Prize winner in Chemistry, Michael Levitt, PhD, at Stanford Faculty of Medication, amongst its scientific advisors. (queenofarticle.com)
  • The Firm has gained quite a few awards, together with the AI 100 Award from CB Insights, the Fierce 15, Frost & Sullivan Greatest Practices Award, NVIDIA Prime 5 AI for Social Influence, Hong Kong Enterprise Expertise Award, and was named one of many Prime 6 Biotechs in AI Drug Discovery by Inside Precision Medication. (queenofarticle.com)
  • Insilico Medication, a medical stage end-to-end synthetic intelligence (AI)-driven drug discovery firm, is connecting biology, chemistry, and medical trials evaluation utilizing next-generation AI techniques. (queenofarticle.com)
  • This review provides an overview of the recent applications of geometric deep learning in bioorganic and medicinal chemistry , highlighting its potential for structure-based drug discovery and design. (bvsalud.org)
  • The current challenges and opportunities are highlighted, and a forecast of the future of geometric deep learning for drug discovery is presented. (bvsalud.org)
  • Following the discovery of a novel series of phosphate-containing small molecular Pin1 inhibitors, the drug design strategy shifted to replacement of the phosphate group with an isostere with potential better pharmaceutical properties. (rcsb.org)
  • While medications used for treating inflammatory disease accounted for just 0.7 per cent of claims across Telus Health's Canadian block of business in 2021, they represent the largest percentage of eligible drug costs at 12.6 per cent, due to the prevalence of high-cost treatments in this drug class. (benefitscanada.com)
  • Discussion in ' Boat Design ' started by bhanu prakash , Dec 16, 2021 . (boatdesign.net)
  • Computational drug design - often called computer-aided drug design - refers to the drug invention process that relies on computer modeling techniques. (nfcr.org)
  • Artificial intelligence in de novo design drives the generation of meaningful new biologically active molecules towards desired properties. (mdpi.com)
  • The region of the GPCR structure that sticks out of the membrane interacts with drugs and other molecules to signal to partner proteins inside the cell. (scripps.edu)
  • Most successful drugs are small organic molecules in the past, while, biopolymer-based, protein-based drugs, mRNA-based and CRISPR-based drugs have become increasingly common recently. (utoronto.ca)
  • Whereas a typical ML approach will search for drug molecules based on intrinsic features such as molecular shape and structure, TML speeds up the process by checking what other ML models convey about a particular molecule. (scienceboard.net)
  • Recombinant DNA technology allowed us to go beyond chemical compounds and design medicines based on the proteins and other large molecules that govern biology. (amgen.com)
  • Drugs that can accomplish this same trick are called PROTAC ® molecules (proteolysis targeting chimeras). (amgen.com)
  • It stated that the successful design of DSP-0038 demonstrates how AI can be used to design selective molecules with dual activity. (europeanpharmaceuticalreview.com)
  • Our goals will be not only to characterize the above interaction from the structure and function point of view, but mainly to design molecules that will "inhibit" these lectins and will, therefore, exhibit pharmacological effects. (muni.cz)
  • 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. (bvsalud.org)
  • He was named "design conference ambassador" for the second year in a row for the upcoming IMDC, and has recently lectured on design at the Polish and Danish War Colleges, the Canadian Forces College, NATO Schools at Oberammergau, the National Counterterrorism Center, the IBM capstone SPADE conference for NATO in Copenhagen, as well as numerous Special Operations and strategic level defense assets in 2018. (smallwarsjournal.com)
  • Covalent allosteric modulators possess the pharmacological advantages (high potency, extended duration of action and low drug resistance) of covalent ligands and the additional benefit of the higher specificity and lower toxicity of allosteric modulators. (drugdiscoverytoday.com)
  • Moreover, patients treated with this drug develop resistance within a few months of treatment. (technologynetworks.com)
  • By evolving C. auris and C. glabrata in different drugs and mapping their responses to other drugs, we have discovered collateral sensitivity (CS) and cross resistance (XR). (jpiamr.eu)
  • CS is the process in which the acquisition of drug resistance towards one drug, confers an increased sensitivity towards another drug. (jpiamr.eu)
  • In this study, we will explore novel treatment schemes that have the potential to prevent the development of antifungal drug resistance in MDR species of most concern: C. auris and C. glabrata. (jpiamr.eu)
  • Aaron Storms] So, the first concept is that flu viruses can become resistant to antiviral medications, and antiviral resistance means that a virus has changed in such a way that the antiviral drug isn't effective or is less effective. (cdc.gov)
  • Aaron Storms] Resistance of influenza A viruses to antiviral drugs can occur spontaneously or it can emerge during the course of antiviral treatment. (cdc.gov)
  • Aaron Storms] For now, the levels of oseltamivir resistance in pandemic H1N1 remain very low, so the recommendations for the use of oseltamivir or zanamivir, another antiviral drug that can be used to treat flu, remain unchanged. (cdc.gov)
  • Aaron Storms] Most of (the) oseltamivir resistance that we're finding in pandemic H1N1 viruses is not associated with drug use. (cdc.gov)
  • Inappropriate prescribing of antibiotics and lack of infection control actions can contribute to drug resistance and put patients at risk for deadly diarrhea (caused by C. difficile ). (cdc.gov)
  • The purpose of this survey was to estimate the prevalence of viral load (VL) suppression and emergence of HIV drug resistance (HIVDR) among individuals receiving antiretroviral therapy (ART) for 36 months or longer in Viet Nam using a nationally representative sampling method. (who.int)
  • 1 The HIV epidemic of viral load (VL) suppression and HIV drug resistance in Viet Nam remains concentrated primarily (HIVDR) patterns at the national scale were unknown. (who.int)
  • According to HIV sentinel surveillance, the HIV a national y representative estimate of VL suppression prevalence was 11.0% in PWID, 2.7% in FSW and and acquired HIV drug resistance (ADR). (who.int)
  • Somerset, N.J. - June 24, 2014 - Redwood Bioscience and Catalent Pharma Solutions, the leading global provider of advanced delivery technologies and development solutions for drugs, biologics and consumer health products, today announced the results of an in vivo toxicology study, demonstrating that an Antibody Drug Conjugate (ADC) generated using the proprietary SMARTag™ platform has a better toxicity profile than a conventional ADC. (catalent.com)
  • Potency, Efficacy, and Effectiveness Drugs affect only the rate at which existing biologic functions proceed. (msdmanuals.com)
  • Quantitative Systems Pharmacology (QSP) software providing the ability to predict the efficacy of drugs being developed to treat idiopathic pulmonary fibrosis (IPF. (simulations-plus.com)
  • Custom QSP software for predicting efficacy & guiding design. (simulations-plus.com)
  • IKS01 has been designed to be sufficiently potent to have target-dependent efficacy even in tumors with low or moderate expression of the target antigen. (esmo.org)
  • Initially, drug-eluting stents (DES) were compared to bare-metal stents (BMS) for efficacy. (medscape.com)
  • The gastro-retentive dosage form to maintain the sustain drug delivery, which would improve the maximum therapeutic efficacy and patient compliance. (who.int)
  • The Oxford-led study is investigating the tolerability and efficacy of PORT-2, a drug that was developed to target iKT and trigger a cancer-specific B and T-cell response to tumours. (ox.ac.uk)
  • These clinical studies were being conducted to evaluate the safety and efficacy of drug products, and you were the principal investigator for these studies. (fda.gov)
  • In this paper the team from Roche discuss use cases where computational methods, including data driven and experimental insights provided by the CSD, have been pivotal in the drug design phase. (cam.ac.uk)
  • Conceptually, the solvation cages in the membranes are analogous to the biological binding site targeted by small molecule drugs. (nersc.gov)
  • Joint research between Exscientia and Sumitomo Dainippon Pharma designed DSP-0038 to be a single small molecule that exhibits high potency as an antagonist for the 5-HT2A receptor and agonist for the 5-HT1A receptor, whilst selectively avoiding similar receptors and unwanted targets, such as the dopamine D2 receptor. (europeanpharmaceuticalreview.com)
  • Our novel approach to drug design and delivery addresses current challenges associated with both large and small molecule therapeutics and represents a fundamental advancement in the field of intracellular biologics. (biospace.com)
  • Published in Drug and Alcohol Dependence (2022). (addiction-ssa.org)
  • Beta Blockers May Avert Cancer-Drug Cardiotoxicity - Medscape - Jun 14, 2022. (medscape.com)
  • As a result, the multi-objective optimization in terms of drug safety, selectivity, stability and affinity poses grand challenges to mathematics, biology, bioengineering and biotechnology. (utoronto.ca)
  • To design successful drugs, it takes collaborative efforts from biologists, biochemists, computer scientists and mathematicians to come up with better homology modeling, efficient structural optimization, rapid molecular docking, fast sampling, linear-scaling quantum algorithms, robust statistical analysis and advanced de novo design. (utoronto.ca)
  • This work showed that the use of these techniques improves satisfaction, effectiveness and efficiency in an alert system for drug-drug interactions, a fact that was evident in specific situations such as the decrease of errors to meet the specified task, the time, the workload optimization and users overall satisfaction with the system. (itba.edu.ar)
  • Flu viruses are constantly undergoing genetic changes and the changes that make a virus resistant can occur without exposure to an antiviral drug. (cdc.gov)
  • Treatment with a flu antiviral drug is recommended for patients who are hospitalized or have severe or progressive illness due to confirmed or suspected flu infection. (cdc.gov)
  • Drug design is the process of finding and testing new treatments based on biological targets. (nfcr.org)
  • A new approach is to apply molecular mechanism towards entire proteomes, enzyme pathways/families (e.g. catecholamine biosynthesis, botulinum neurotoxins), and high value drug targets, including G-protein coupled receptors (GPCRs). (utoronto.ca)
  • We are now at the start of a fourth wave that will radically alter our concept of how drugs can work, paving the way for new treatments aimed at thousands of disease targets now viewed as "undruggable. (amgen.com)
  • In the 1970s, Wave 2 introduced rational drug design-specific compounds aimed at specific molecular targets that play a role in disease. (amgen.com)
  • By inducing proximity between their targets and these mechanisms, multispecifics can harness the awesome power of biology to go well beyond what conventional drugs can accomplish. (amgen.com)
  • Mohapatra P. K., Satyavani C. H., Sahoo S.. The Design And Development Of Carvedilol Gastroretentive Floating Drug Delivery Systems Using Hydrophilic Polymers And In Vitro Characterization. (who.int)
  • Effective prevention of NIHL with drug agents would reduce the prevalence of NIHL. (cdc.gov)
  • Overview of Adverse Drug Reactions Adverse drug reactions (adverse effects) are any unwanted effects of a drug. (msdmanuals.com)
  • ABSTRACT The Maltese Medicines Authority was tasked with developing a reporting form that captures high-quality case information on adverse drug reactions (ADRs) and medication errors in order to fulfil its public-health obligations set by the European Union (EU) legislation on pharmacovigilance. (who.int)
  • If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online ( http://www.fda.gov/Safety/MedWatch ) or by phone (1-800-332-1088). (medlineplus.gov)
  • Purpose: To compare the accuracy and precision of a conventional intraocular syringe to the Suh precision syringe (SPS), a new injection device designed to decrease operator error and to reduce adverse outcomes by providing a more ergonomic technique for periocular and intraocular injections. (mendeley.com)
  • Adverse effects from drugs taken as directed and infections resulting from drug use are not included. (cdc.gov)
  • Please do not use this form to submit personal or patient medical information or to report adverse drug events. (medscape.com)
  • You are encouraged to report adverse drug event information to the FDA. (medscape.com)
  • 35. Väänänen K. Mechanism of osteoclast mediated bone resorption: rationale for the design of new therapeutics. (bvsalud.org)
  • Only 10-14% of drug candidates entering clinical trials actually reach the market as medicines, with an estimated US$2-3 billion price tag for each new treatment 3 . (nature.com)
  • Under the Act, a pharmaceutical manufacturer must apply to FDA for approval to market new drugs and is required to demonstrate, often through clinical trials, that a drug is safe and effective before receiving approval to market a drug. (fda.gov)
  • Initial articles in this special issue describe common pre-clinical (animal) testing paradigms used to assess potential otoprotective drug agents and design-related factors that impact translation of promising agents into human clinical trials. (cdc.gov)
  • The design of analgesic clinical trials / editors, Mitchell B. Max, Russell K. Portenoy, Eugene M. Laska. (who.int)
  • Drugs reported in NAMCS and NHAMCS are coded twice: first "as entered" on the survey data collection form, using an NCHS-assigned 5-digit code, and second using a corresponding 6-digit generic-equivalent code based on the Multum classification. (cdc.gov)
  • It is important to note that the drug database as well as the Multum classification can change over time. (cdc.gov)
  • For the database, this can occur when a drug that was not previously assigned a code by the Multum classification is added to that classification and its DRUGID value in the ACDD is then changed to reflect the new Multum designation. (cdc.gov)
  • When selecting drug therapeutic categories, please note that not all therapeutic categories have second or third levels in the classification scheme. (cdc.gov)
  • Drag and drop your protein, or search comfortably in an online database. (biosolveit.de)
  • The search for new drugs that control the continuous relapses of multiple myeloma is still required. (nih.gov)
  • Drugs that were found in the 2015 NAMCS and 2015 NHAMCS Emergency Department public use files will show up with an estimate in the search results. (cdc.gov)
  • Fill out the form below to search the database for a list of drugs matching your search criteria. (cdc.gov)
  • Abnormal biochemical and cellular changes caused by disease are identified, and then compounds that may specifically prevent or correct these abnormalities (by interacting with specific sites in the body) can be designed. (msdmanuals.com)
  • Under 21 CFR 312.62(b), a clinical investigator is required to maintain adequate and accurate case histories relating to the clinical use of investigational new drugs, including case report forms and supporting data such as the medical records of individuals administered the investigational drug or employed as a control in the investigation. (fda.gov)
  • Scientists at The Scripps Research Institute (TSRI) have peered deep into the heart of a key protein used in drug design and discovered dynamic structural features that may lead to new ways to target diseases. (scripps.edu)
  • The approach in the new study enabled researchers to follow the effects of drug binding at the extracellular surface on changes in protein structure and dynamics at the intracellular surface-the structural basis of signal transfer-across the heart of the GPCR. (scripps.edu)
  • The protein F3, designed to adhere to cancer cells and transport into the cells' nuclei, is tethered to the surface of the structures. (pharmtech.com)
  • The main reason allosteric sites are of such interest to drug design is that they can be used to inhibit or improve the activity of a protein, eg. (news-medical.net)
  • The determination of the three-dimensional structure of RAF1 is a key step towards this goal, because it reveals the parts of the protein to which a drug could be chemically anchored, and promote its destruction by the cellular machinery (cells have cleaning mechanisms that degrade defective or useless proteins). (technologynetworks.com)
  • Redwood Bioscience is developing a precision protein-chemical engineering technology to produce next-generation antibody-drug conjugates and other semi-synthetic biotherapeutics. (catalent.com)
  • Despite being a low-abundance amino acid, cysteine plays an essential role in regulating protein function and serves as a satisfactory target of post-translational modifications and drug developments. (bvsalud.org)
  • Quantitative Systems Toxicology (QST) software designed to be used during drug development to provide deeper insight into the mechanisms responsible for observed drug-induced liver injury (DILI) responses. (simulations-plus.com)
  • Quantitative Systems Toxicology (QST) software for predicting and understanding drug-induced kidney injury. (simulations-plus.com)
  • NMS Labs has designed a DUID toxicology panel that covers the seven DRE drug categories and all the priority drug groups recognized by the National Highway Traffic Safety Administration (NHTSA). (nmslabs.com)
  • The ProofPOSITIVE ® Drug Impaired Driving/DRE Toxicology Panels are available with or without alcohol testing. (nmslabs.com)
  • The results published today in Molecular Cell open up a window of opportunity to design RAF1 degraders that, either alone or in combination with KRAS inhibitors, could generate an important therapeutic effect in patients with lung adenocarcinoma induced by KRAS oncogenes. (technologynetworks.com)
  • up to 4 therapeutic classes can be assigned per drug in NAMCS and NHAMCS. (cdc.gov)
  • For example, a drug that was assigned to only a second-level therapeutic category in one year may now be assigned to a new third-level category. (cdc.gov)
  • If a data user is looking for drugs over time, it is important to also check that drug's identifying information as well as Multum's therapeutic category structure in the public use file documentation for the earlier years, in order to ensure that the correct codes are being selected. (cdc.gov)
  • During the rapid development of redox-responsive polymers, molecular design and related synthetic methodology plays a crucial role. (rsc.org)
  • Read the full paper - A Real-World Perspective on Molecular Design (B. Kuhn et al. (cam.ac.uk)
  • Emphasis is placed on molecular property prediction, ligand binding site and pose prediction, and structure-based de novo molecular design. (bvsalud.org)
  • If readers are unfamiliar with Army Design Methodology, they should refer to U.S. Army Field Manual 5-0, Operations, Chapter 3 or Field Manual 3-24, Counterinsurgency, Chapter 4. (smallwarsjournal.com)
  • In 2007, drug-induced deaths were more common than alcohol-induced or firearm-related deaths in the United States ( 1 ). (cdc.gov)
  • Educational Sanctions are learning opportunities, including, but not limited to, written papers, drug and alcohol education, and program attendance, designed to be completed by the Student. (salisbury.edu)
  • Both alcohol (BAC - Blood Alcohol Content) and drug impairment (DUID) are responsible for thousands of traffic accidents each year. (nmslabs.com)
  • Regardless of thinking that you are an abuser of marijuana, alcohol, opiates and other drugs, you can rely over FDA approved cleansing products. (passhairdrugtest.com)
  • According to the research team, the study in mice is the first single nanomaterial used to simultaneously deliver a drug and provide multimode imaging of a disease tissue in a live animal. (pharmtech.com)
  • Taking advantage of the physiological signals, redox-responsive polymeric drug carriers constitute a significant research area in the various stimuli-responsive polymers for biomedical applications. (rsc.org)
  • Recently, nano-bio engineering and technology for drug transport and drug delivery have emerged as an important area of research. (utoronto.ca)
  • The new approach, dubbed "transformation machine learning" (TML) by the research team, made better predictions than traditional ML in three domains that address scientific problems, including drug design. (scienceboard.net)
  • Do you have a unique perspective on your research related to drug design or machine learning? (scienceboard.net)
  • To avoid that lack of perceived commercial perspective will leave existing medical needs unmet, pharmaceutical companies and many other stakeholders are discussing ways to improve the efficiency of drug Research and Development. (frontiersin.org)
  • And so, the latest piece of research on drug consumption rooms is a relief. (addiction-ssa.org)
  • Beyond the development of drugs against KRAS, one of the most active research areas at the moment seeks to identify inhibitors of proteins, such as RAF1, responsible for transmitting the KRAS oncogenic signals. (technologynetworks.com)
  • A research design in which participants first experience the baseline condition (A), then experience the experimental treatment (B), and then return to the baseline (A). (learner.org)
  • To trace the filaments, the research team designed a computer algorithm informed by slime-mold behavior. (scitechdaily.com)
  • If you are considering the use of Halotestin bodybuilding supplement , you need to do your initial research about this drug to ensure that you are making the right choices. (healthstatus.com)
  • To that end, in 1985, the National Center for Health Statistics (NCHS) created the Questionnaire Design Research Laboratory (QDRL). (cdc.gov)
  • The 546-patient trial showed that the experimental drug resulted in greater and sustained improvements in glycemic control and sustained reductions in body weight compared to placebo, according to Cliff Bailey, head of diabetes research at Aston University, in Birmingham, England, and the study's lead investigator. (medscape.com)
  • Most of the money spent on a drug is on marketing, not research. (abovetopsecret.com)
  • Methods: A qualitative, exploratory, descriptive research design was employed to conduct psychosocial and health screenings of children and their families. (bvsalud.org)
  • In drug design, we found that TML provided insight into drug target specificity, the relationships between drugs, and the relationships between target proteins," wrote the authors, led by Ivan Olier of the School of Computer Science and Mathematics at John Moores University in the U.K. (scienceboard.net)
  • In biopharma pipelines across the industry, we're seeing more investigational multispecific drugs that can form connections with two or more proteins. (amgen.com)
  • Structure-based drug design uses three-dimensional geometric information of macromolecules, such as proteins or nucleic acids , to identify suitable ligands . (bvsalud.org)
  • Neuraminidase are the proteins that allow flu viruses to escape infected cells, and for that reason, antiviral drugs that block neuraminidase proteins, like oseltamivir, help to limit further infection. (cdc.gov)
  • It's better at choosing drugs than humans are -- and without the best science, we won't get the best results. (scienceboard.net)
  • During drug development, standard or average doses are determined. (msdmanuals.com)
  • Drug development faces the double challenge of increasing costs and increasing pressure on pricing. (frontiersin.org)
  • Speakers and participants at the symposium were convinced that appropriate use of the above new options may indeed help to increase the efficiency of future drug development. (frontiersin.org)
  • The difference between the two estimates is largely driven by attrition, i.e., the inclusion of costs for drugs that failed in development. (frontiersin.org)
  • Clayco completed construction on a distribution facility for Longs Drug Stores Corporation, the latest tenant in a new commercial development, KeyStone Pacific Business Park, located in the San Joaquin Valley, east of the San Francisco Bay area. (claycorp.com)
  • One of the main challenges in oncology is the development of drugs against KRAS oncogenes. (technologynetworks.com)
  • ADME-enabling technologies for drug design and development. (cdc.gov)
  • Cytel recently conducted a webinar on Bayesian Dose-finding Designs for Modern Drug Development, presented by Dr. (cytel.com)
  • Catalent Pharma Solutions is the leading global provider of advanced delivery technologies and development solutions for drugs, biologics and consumer health products. (catalent.com)
  • The trial of DSP-0038, an Alzheimer's disease psychosis drug designed using artificial intelligence, will assess its ability to improve the behavioural and psychological symptoms of dementia. (europeanpharmaceuticalreview.com)
  • The world's first Alzheimer's disease (AD) drug candidate designed by artificial intelligence (AI) will soon enter a first-in-human Phase I clinical trial in the US. (europeanpharmaceuticalreview.com)
  • The NIOSH List is an aid designed to enable employers to identify which drugs routinely handled by employees are considered by NIOSH to be hazardous drugs. (cdc.gov)
  • The List is intended to be used in conjunction with NIOSH's risk management recommendations (hyperlink) to assist employers in establishing hazardous drug management procedures specific to their workplace. (cdc.gov)
  • Overall business productivity depends upon efficient working activity of workers but if they are under intoxicating effects of drugs, they are of no use for the employers. (passhairdrugtest.com)
  • Although KRAS oncogenes were already discovered by Mariano Barbacid's group four decades ago, the first drug against them -Sotorasib, Amgen- has been approved by the FDA only a year ago. (technologynetworks.com)
  • Thankfully, working with designs and assets created in illustrator won't break your workflow, as it's simple to open these files and convert them into XD content. (adobe.com)
  • It contains both design and source views allowing developers to view content identical to the end result while the interface is being created. (eclipse.org)
  • SeeSAR fosters innovation during every step of your drug design process. (biosolveit.de)
  • It is typically an iterative process between a lead structure that is refined to yield the final drug and the pre-clinical testing. (meilerlab.org)
  • Whether you're working with logo assets and icons or intricate vector illustrations, integrations between Adobe illustrator and Adobe XD unlock powerful workflows for editing and managing vector assets throughout the design process. (adobe.com)
  • Once you're happy with your design, the checkout process is simple. (musthavemenus.com)
  • Some of them adopt recommended detoxification ways to go through the drug screening process while majority of drug abusers stumble upon Cheating On Drug Test. (passhairdrugtest.com)
  • After getting Clean Drug Test Tips, you can perform drug screening process at your home without disturbing privacy. (passhairdrugtest.com)
  • Detoxification process flushes out drug substances from system simultaneously increasing your confidence of donating Clean Pee to the recommended lab. (passhairdrugtest.com)
  • Groups consider concepts such as lift, drag, thrust, and buoyancy as they test their vehicles. (lessonplanet.com)
  • The vision to design this desirable Bugatti is to have a street-legal race car that has the signature Chiron DNA, still being lightweight and overshadowing the "C" design element customary to the fastest Bugatti ever. (yankodesign.com)
  • Prescribed drugs eventually supplanted illicit drugs as the leading cause of drug-related overdose deaths ( 3 ). (cdc.gov)
  • The National Education Association Health Information Network is set to release a resource guide designed to help educators teach students about prescription drug abuse and misuse. (drugtopics.com)
  • Members of racial/ethnic minorities might have been less affected by this change because they are less likely to use prescription drugs and therefore might have been less likely to misuse such drugs ( 4 ). (cdc.gov)
  • These include pharmaceuticals (e.g. antiviral drugs, antibiotics), and critical materiel (personal protective equipment including respiratory protective equipment, and ventilators). (cdc.gov)
  • We tested the neuraminidase drug sensitivity of clade compared with clade 1 viruses (Table 1, Figure, panel B). (cdc.gov)
  • Boat Design Net does not necessarily endorse nor share the view of each individual post. (boatdesign.net)
  • The 32-year-old, nicknamed 'El Raton' (The Mouse), has allegedly helped to run his father's drug trafficking operations since El Chapo was extradited to the United States in 2017. (yahoo.com)
  • The seizure drug is meant to be customized for high dosage treatments, and was developed with Aprecia's ZipDose technology. (thenextweb.com)
  • In work spearheaded by TSRI's Matthew Eddy, PhD, first author of the new study, the researchers used NMR to observe A 2a AR in many different conformations, shedding light on how it changes shape on the surface of human cells in response to drug treatments. (scripps.edu)
  • Generally speaking, an allosteric drug would also be used at a comparatively lower dose than a drug acting directly on the protein's active site, thus providing more effective treatments with fewer side effects. (news-medical.net)
  • To examine trends and assess drug-induced deaths during 2003--2007 in the United States, CDC analyzed data from the mortality component of the National Vital Statistics System. (cdc.gov)
  • While the immediate impact of these advances on drug approvals may be limited, there is proof of concept for early recognition of potential side-effects, successful drug repurposing, improved accuracy for drug property predictions, and the autonomous generation of drug candidates by machine intelligence. (nature.com)
  • Computational drug design has been significantly improved by advances in algorithms, large amounts of data and improved technology. (nfcr.org)
  • Here, we review the recent advances in the design of covalent allosteric modulators with an emphasis on successful examples. (drugdiscoverytoday.com)
  • The aim of this work was to investigate the feasibility of manufacturing immediate-release dosage forms with customised designs and drug combinations, using fused deposition modelling 3D Printing. (bl.uk)
  • Provided that the clinical work is carried out, this work has paved the way to manufacture individualised doses and bespoke designs of dosage forms in an economical way. (bl.uk)
  • Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS , dosage analysis, or drug administration analysis. (bvsalud.org)
  • We analyzed cohorts using case-crossover and self-controlled case series designs evaluating exposure to the precipitant drug within person-time exposed to the object drug. (harvard.edu)
  • With heavy event-dependent drug discontinuation, a case-crossover design may be preferable provided there are no time-related trends in drug exposure. (harvard.edu)
  • Conversely, XR confers reduced susceptibility to more than one drug upon exposure to one drug. (jpiamr.eu)
  • While otoprotective drugs will ultimately be developed for use by specific noise -exposed populations, there has been little effort to develop pre-clinical (animal) models that accurately model exposure hazards across diverse human populations. (cdc.gov)
  • BACKGROUND: Self-controlled designs, both case-crossover and self-controlled case series, are well suited for evaluating outcomes of drug-drug interactions in electronic healthcare data. (harvard.edu)
  • 50%), self-controlled case series may be preferable to case-crossover design for evaluating outcomes of drug-drug interactions. (harvard.edu)
  • For starters, a conventional drug only works for as long as it's binding to its target. (amgen.com)
  • METHODS: We simulated cohorts of patients exposed to two drugs: a chronic drug (object) and a short-term drug (precipitant) with an associated interaction of 2.0 on the odds ratio scale. (harvard.edu)
  • Drug-induced deaths include all deaths for which drugs are the underlying cause ( 1 ), including deaths attributable to acute poisoning by drugs (drug overdoses) and deaths from medical conditions resulting from chronic drug use. (cdc.gov)
  • Brake design specialists AirBack has introduced a drag-free brake design that the company claims significantly improves braking efficiency. (pmw-magazine.com)
  • Flagship machine learning platform for ADMET modeling with extended capabilities for data analysis, metabolism prediction, high-throughput pharmacokinetic simulation (HTPK), and AI-driven drug design. (simulations-plus.com)
  • In silico prediction of drug-induced ototoxicity using machine learning and deep learning methods. (cdc.gov)
  • Christie says that the health plans can take every innovation they like to the table, from newly adopted narrow - or high-performing - networks to accountable care organizations, without having to design each offering for a self-insured company's likes and dislikes. (managedcaremag.com)
  • Multispecific drugs herald a new era of biopharmaceutical innovation. (amgen.com)
  • Ben Zweibelson is the Program Director for Design and Innovation at the Joint Special Operations University and is a doctoral student at Lancaster University. (smallwarsjournal.com)
  • Innovation in trial designs are offering new routes forward for organizations of any size. (cytel.com)
  • Two details in A 2a AR's structure gave researchers insight into how future drugs could manipulate the receptor. (scripps.edu)
  • Researchers from the University of California San Diego, UCÂ Santa Barbara, and MIT have developed nanometer-sized hybrid structures carrying anti-cancer drugs and quantum dot imaging agents. (pharmtech.com)
  • San Diego, CA (Sept.11)- Researchers from the University of California (UC) San Diego, UC Santa Barbara, and the Massachusetts Institute of Technology have developed nanometer-sized hybrid structures carrying anticancer drugs and quantum-dot imaging agents. (pharmtech.com)
  • Now, as reported today in the journal Nature , researchers have designed a polymer membrane with molecular cages built into its pores that hold positively charged ions from a lithium salt. (nersc.gov)
  • The researchers designed a computer algorithm inspired by the organism's behavior and applied it to data containing the positions of 37,000 galaxies ("food" for the slime mold) mapped by the Sloan Digital Sky Survey. (scitechdaily.com)
  • The synthetic iNKT agonists are designed to optimally engage the T-cell receptor on the iNKT and facilitate its binding to dendritic cells, resulting in the secretion of a large amount of pro-inflammatory cytokines. (ox.ac.uk)
  • The results represent the first attempt to design PDCs composed of stabilized peptide inhibitors and GRL0617 to inhibit PLpro. (bvsalud.org)
  • Dock, design, and analyze your compound in a flash, with swift and informative calculations. (biosolveit.de)
  • Since drag-racing tires have a softer compound than typical street tires, you would think that softer is better. (cartechbooks.com)
  • Here, we employ DNA nanotechnology to design a synthetic enzyme that substantially outperforms its biological archetypes. (nature.com)