The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
Presentations of summary statements representing the majority agreement of physicians, scientists, and other professionals convening for the purpose of reaching a consensus--often with findings and recommendations--on a subject of interest. The Conference, consisting of participants representing the scientific and lay viewpoints, is a significant means of evaluating current medical thought and reflects the latest advances in research for the respective field being addressed.
Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals.
Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.
Species of the genus LENTIVIRUS, subgenus primate immunodeficiency viruses (IMMUNODEFICIENCY VIRUSES, PRIMATE), that induces acquired immunodeficiency syndrome in monkeys and apes (SAIDS). The genetic organization of SIV is virtually identical to HIV.
Vaccines or candidate vaccines designed to prevent SAIDS; (SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME); and containing inactivated SIMIAN IMMUNODEFICIENCY VIRUS or type D retroviruses or some of their component antigens.
Process that is gone through in order for a drug to receive approval by a government regulatory agency. This includes any required pre-clinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance of the drug.
Acquired defect of cellular immunity that occurs naturally in macaques infected with SRV serotypes, experimentally in monkeys inoculated with SRV or MASON-PFIZER MONKEY VIRUS; (MPMV), or in monkeys infected with SIMIAN IMMUNODEFICIENCY VIRUS.
A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans.
INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally, and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown.
A genus of FLAVIVIRIDAE causing parenterally-transmitted HEPATITIS C which is associated with transfusions and drug abuse. Hepatitis C virus is the type species.
INFLAMMATION of the LIVER in humans that is caused by HEPATITIS C VIRUS lasting six months or more. Chronic hepatitis C can lead to LIVER CIRRHOSIS.
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
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)
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.
Antibodies to the HEPATITIS C ANTIGENS including antibodies to envelope, core, and non-structural proteins.
An organoplatinum compound that possesses antineoplastic activity.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
Organic compounds which contain platinum as an integral part of the molecule.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.
A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.
Dimers found in DNA chains damaged by ULTRAVIOLET RAYS. They consist of two adjacent PYRIMIDINE NUCLEOTIDES, usually THYMINE nucleotides, in which the pyrimidine residues are covalently joined by a cyclobutane ring. These dimers block DNA REPLICATION.
All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.
A publication issued at stated, more or less regular, intervals.
A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.
Lists of persons or organizations, systematically arranged, usually in alphabetic or classed order, giving address, affiliations, etc., for individuals, and giving address, officers, functions, and similar data for organizations. (ALA Glossary of Library and Information Science, 1983)
A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. Although they take part in the assembly process, molecular chaperones are not components of the final structures.
A class of MOLECULAR CHAPERONES whose members act in the mechanism of SIGNAL TRANSDUCTION by STEROID RECEPTORS.
The process of finding chemicals for potential therapeutic use.
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 systematic study of the complete complement of proteins (PROTEOME) of organisms.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Use for articles on the investing of funds for income or profit.
A genus of fungi in the family Ophiostomataceae, order OPHIOSTOMATALES. Several species are the source of Dutch elm disease, which is spread by the elm bark beetle.
Organizations representing specialized fields which are accepted as authoritative; may be non-governmental, university or an independent research organization, e.g., National Academy of Sciences, Brookings Institution, etc.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC
The type species of SIMPLEXVIRUS causing most forms of non-genital herpes simplex in humans. Primary infection occurs mainly in infants and young children and then the virus becomes latent in the dorsal root ganglion. It then is periodically reactivated throughout life causing mostly benign conditions.
A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. (Dorland, 27th ed.)
A genus of the family HERPESVIRIDAE, subfamily ALPHAHERPESVIRINAE, consisting of herpes simplex-like viruses. The type species is HERPESVIRUS 1, HUMAN.
An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower.
Cell-surface proteins that bind histamine and trigger intracellular changes influencing the behavior of cells. Histamine receptors are widespread in the central nervous system and in peripheral tissues. Three types have been recognized and designated H1, H2, and H3. They differ in pharmacology, distribution, and mode of action.
An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.
A class of histamine receptors discriminated by their pharmacology and mode of action. Most histamine H1 receptors operate through the inositol phosphate/diacylglycerol second messenger system. Among the many responses mediated by these receptors are smooth muscle contraction, increased vascular permeability, hormone release, and cerebral glyconeogenesis. (From Biochem Soc Trans 1992 Feb;20(1):122-5)
A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H3 receptors were first recognized as inhibitory autoreceptors on histamine-containing nerve terminals and have since been shown to regulate the release of several neurotransmitters in the central and peripheral nervous systems. (From Biochem Soc Trans 1992 Feb;20(1):122-5)
Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically.
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.
A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H2 receptors act via G-proteins to stimulate ADENYLYL CYCLASES. Among the many responses mediated by these receptors are gastric acid secretion, smooth muscle relaxation, inotropic and chronotropic effects on heart muscle, and inhibition of lymphocyte function. (From Biochem Soc Trans 1992 Feb;20(1):122-5)

Electronic volume analysis of L1210 chemotherapy. (1/6280)

The rapid analysis of in vivo chemotherapy on the L1210 ascites tumor grown in C57BL/6 X DBA/2F1 mice has been shown by means of an electronic volume analysis. The drugs were injected on the 4th day of tumor growth, and the cells in the peritoneal cavity were studied at 24-hr intervals on the 5th through 7th day. Using the electronic cell volume distributions, combined with labeling indices, cell morphology, and cell counts, it was found that the alkylating agents. 1,3-bis(2-chloroethyl)-1-nitrosourea and cyclophosphamide, at the dosages used, were more effective than the S-phase-specific drugs, palmitoyl ester of 1-beta-D-arabinofuranosylcytosine, vincristine, and methotrexate.  (+info)

Fluorimetric multiparameter cell assay at the single cell level fabricated by optical tweezers. (2/6280)

A fluorimetric multi-parameter cell sensor at the single cell level is presented which makes it possible to observe the physiological behavior of different cell lines, different physiological parameters, and statistical data at the same time. Different cell types were immobilized at predefined positions with high accuracy using optical tweezers and adhesion promoting surface layers. The process is applicable to both adherent and non-adherent cells. Coating of the immobilization area with mussel adhesive protein was shown to be essential for the process. Intracellular proton and calcium concentrations in different cell classes were simultaneously imaged and the specific activation of T lymphocytes was demonstrated. This method should be especially useful for drug screening due to the small sample volume and high information density.  (+info)

Immunising potency of Leptospira interrogans serotype canicola after heat inactivation at different temperatures. (3/6280)

The immunogenicity of Leptospira interrogans serotype canicola suspensions inactivated by various degrees of heat exposure was examined in hamsters. No differences between leptospires killed at 50 degrees C and at 98 degrees C were shown. After exposure to 121 degrees C, suspensions retained their ability to protect against lethal infections but lost their ability to prevent leptospiruria. Tests with vaccines inactivated at or below 98 degrees C showed that the doses required for complete protection varied with the interval between vaccination and challenge. Larger doses were required to prevent the development of leptospiruria than to prevent death.  (+info)

Screening of Korean forest plants for rat lens aldose reductase inhibition. (4/6280)

Naturally occurring substances which can prevent and treat diabetic complications were sought by examining ethanol extracts prepared from Korean forest plants for their inhibitory effects on rat lens aldose reductase activity in vitro. Among the plants examined, Acer ginnala, Illicium religiosum and Cornus macrophylla exerted the most strong inhibitory activity on aldose reductase.  (+info)

Micronucleus test using cultured new born rat astrocytes. (5/6280)

Micronuclei is induced in cytoplasm as a consequence of the formation of chromosomal fragments or remaining chromosomes during cell division by the cause of clastogens or spindle poisons, and is used as an indicator of genotoxicity screening tests. There are few short-term genotoxicity screening tests using brain cells. We attempted to establish a new in vitro micronucleus test (MN test) system by use of central nervous system cells. Primary cultured astrocytes were prepared from newborn male Sprague-Dawley (SD) rats. In growth curve of astrocytes, doubling time was determined to be 31 h. In time study, the highest frequency of micronuclei was observed at 48 h, 72 h and 6 h-exposure-66 h-recovery by vincristine (VCR), mitomycin C (MMC) without metabolic activation system and cyclophosphamide (CPM) with metabolic activation system, respectively. Dose-response relationships between micronucleus frequency and concentrations of MMC, VCR and CPM were observed, respectively. It is suggested that the in vitro MN test using new born rat-astrocytes could be used as a screening test of environmental and occupational genotoxic chemicals in the central nervous system cells.  (+info)

Recombinant soluble form of PSGL-1 accelerates thrombolysis and prevents reocclusion in a porcine model. (6/6280)

BACKGROUND: We investigated whether administration of a soluble recombinant P-selectin glycoprotein ligand-1 chimera (rPSGL-Ig) in conjunction with thrombolytic therapy would enhance thrombolysis by preventing ongoing interactions of leukocytes with platelets and the injured arterial wall. METHODS AND RESULTS: An occlusive thrombus was formed in an internal iliac artery of Yorkshire pigs by placement of a copper coil in the artery under fluoroscopic guidance. Pigs then received heparin and, 15 minutes later, either vehicle or rPSGL-Ig followed by infusion with 25 mg tissue plasminogen activator according to the 90-minute regimen. Blood flow through the artery was monitored by angiography and scored on a scale of 0 to 3. Lysis of the thrombus was accelerated by 70% in pigs treated with rPSGL-Ig 250 microg/kg compared with control (13.3+/-5.0 versus 44. 4+/-13.3 minutes; n=9 each). Eight of 9 control pigs reoccluded in 13.8+/-16.9 minutes after the end of tissue plasminogen activator infusion, whereas no reocclusion was observed in 8 of 9 pigs in the rPSGL-Ig group. When the dose of rPSGL-Ig was increased to 500 microg/kg, time to lysis was shortened by 61% from control (18.0+/-8. 4 versus 46.0+/-8.9 minutes). Reocclusion occurred in 6.0+/-15.2 minutes in control but not in any rPSGL-Ig-treated pig (n=5 each). In addition, near-normal flow (score 2 or 3) after thrombolysis was achieved 59% and 58% faster in the 2 rPSGL-Ig groups than in their respective controls. CONCLUSIONS: Inhibition of leukocyte accumulation at the site of thrombosis with rPSGL-Ig may represent a safe therapeutic intervention that could be important in accelerating thrombolysis, achieving optimal reperfusion, and reducing incidence of acute reocclusion.  (+info)

Recovery of the vestibulocolic reflex after aminoglycoside ototoxicity in domestic chickens. (7/6280)

Avian auditory and vestibular hair cells regenerate after damage by ototoxic drugs, but until recently there was little evidence that regenerated vestibular hair cells function normally. In an earlier study we showed that the vestibuloocular reflex (VOR) is eliminated with aminoglycoside antibiotic treatment and recovers as hair cells regenerate. The VOR, which stabilizes the eye in the head, is an open-loop system that is thought to depend largely on regularly firing afferents. Recovery of the VOR is highly correlated with the regeneration of type I hair cells. In contrast, the vestibulocolic reflex (VCR), which stabilizes the head in space, is a closed-loop, negative-feedback system that seems to depend more on irregularly firing afferent input and is thought to be subserved by different circuitry than the VOR. We examined whether this different reflex also of vestibular origin would show similar recovery after hair cell regeneration. Lesions of the vestibular hair cells of 10-day-old chicks were created by a 5-day course of streptomycin sulfate. One day after completion of streptomycin treatment there was no measurable VCR gain, and total hair cell density was approximately 35% of that in untreated, age-matched controls. At 2 wk postlesion there was significant recovery of the VCR; at this time two subjects showed VCR gains within the range of control chicks. At 3 wk postlesion all subjects showed VCR gains and phase shifts within the normal range. These data show that the VCR recovers before the VOR. Unlike VOR gain, recovering VCR gain correlates equally well with the density of regenerating type I and type II vestibular hair cells, except at high frequencies. Several factors other than hair cell regeneration, such as length of stereocilia, reafferentation of hair cells, and compensation involving central neural pathways, may be involved in behavioral recovery. Our data suggest that one or more of these factors differentially affect the recovery of these two vestibular reflexes.  (+info)

Coating titanium implants with bioglass and with hydroxyapatite. A comparative study in sheep. (8/6280)

This study compares the osteointegration of titanium implants coated with bioglass (Biovetro GSB formula) and with hydroxyapatite (HAP). Twenty-four bioglass-coated and 24 HAP-coated cylinders were implanted in the femoral diaphyses of sheep, and examined after 2, 4, 6, 8, 12, and 16 weeks. The HAP coating gave a stronger and earlier fixation to the bone than did bioglass. Bioglass formed a tissue interface which showed a macrophage reaction with little new bone formation activity. In contrast, HPA, showed intense new bone formation, with highly mineralised osseous trabeculae in the neighbourhood of the interface.  (+info)

Preclinical Drug Development | Scientific research info incl meetings, conferences, seminars, symposia,tradeshows,jobs,jobfairs, professional tips and more.
The preclinical pharmacology group provides support for drug discovery and drug development programs at ETC. The group develops establishes and validates in vitro and in vivo pharmacokinetic and metabolic methods to screen and evaluate small molecules and peptides for their drug-like properties.. The group also establishes in vivo disease models to validate potential drugable targets and to evaluate therapeutic properties of preclinical drug candidates.. ...
Seventh Wave Laboratories now offers a battery of gastrointestinal (GI) preclinical models to help clients to assess the behaviour of oral medications.
The clinical utility of proteasome inhibitors as treatment for multiple myeloma and non-Hodgkins lymphoma (NHL) has been validated with two parenterally administered agents: bortezomib, a dipeptide boronate that was approved by the FDA in 2003; and carfilzomib, a tetrapeptide epoxyketone that has shown promising activity in Phase 1 clinical trials. The clinical development of an orally bioavailable proteasome inhibitor would offer improvement in both dosing flexibility and patience convenience over intravenous (IV) administration. Furthermore, oral administration will allow a practical approach to investigating the affect of prolonged proteasome inhibition by repeated daily dosing in patients with advanced malignancies. Here we describe the preclinical pharmacology of PR-047, a tripeptide epoxyketone that was selected through a medicinal chemistry effort designed to find a selective inhibitor of the chymotrypsin-like (CT-L) activity of the proteasome that combined the efficacy and safety of ...
TY - JOUR. T1 - Preclinical pharmacology, ocular tolerability and ocular hypotensive efficacy of a novel non-peptide bradykinin mimetic small molecule. AU - Sharif, Najam A.. AU - Li, Linya. AU - Katoli, Parvaneh. AU - Xu, Shouxi. AU - Veltman, James. AU - Li, Byron. AU - Scott, Daniel. AU - Wax, Martin. AU - Gallar, Juana. AU - Acosta, Carmen. AU - Belmonte, Carlos. PY - 2014/11/1. Y1 - 2014/11/1. N2 - We sought to characterize the ocular pharmacology, tolerability and intraocular pressure (IOP)-lowering efficacy of FR-190997, a non-peptidic bradykinin (BK) B2-receptor agonist. FR-190997 possessed a relatively high receptor binding affinity (Ki=27nM) and a high invitro potency (EC50=18.3±4.4nM) for inositol-1-phosphate generation via human cloned B2-receptors expressed in host cells with mimimal activity at B1-receptors. It also mobilized intracellular Ca2+ in isolated human trabecular meshwork (h-TM), ciliary muscle (h-CM), and in immortalized non-pigmented ciliary epithelial (h-iNPE) cells ...
The Preclinical Pharmacology Core is located in two contiguous labs (L4.244/L4.245) on the 4th floor of the Green Science Building (L Building) within the Biochemistry Department.. ...
Preclinical Drug Discovery () pe Pret: 691.99 lei. These books provide theoretical, practical and troubleshooting guidelines on various aspects o
Molecules, Vol. 25, Pages 429: Pharmacological Overview of the BGP-15 Chemical Agent as a New Drug Candidate for the Treatment of Symptoms of Metabolic Syndrome Molecules doi: 10.3390/molecules25020429 Authors: Pető Kósa Fehér Ujhelyi Sinka Vecsernyés Szilvássy Juhász Csanádi Vígh Bácskay BGP-15 is a n...
In a study published in Nature Communications, researchers at Karolinska Institutet and Uppsala University in Sweden present a new drug candidate, which selectively kills dormant cells within a cancer tumour through starvation. These tumour cells, which are found in less oxygenated parts of solid tumours, are resistant to conventional treatments.
Challenge 1: Redesign Research Pipeline. Clinical trials have yet to reveal an effective therapy for most brain tumours. This harsh reality stems, in part, from an incomplete understanding of brain tumour biology and the existence of a disconnect between preclinical drug development and rigorous testing in the clinic. Each element of the brain tumour research pipeline, from basic neurobiology to clinical trials, requires careful scrutiny and increased investment, although the development of an overarching strategy that facilitates and promotes interdisciplinary research is equally important . This strategy would bring an end to the previous siloed organization of working practices, in which basic and clinical researchers performed their studies independently and collaborated only when laboratory research was judged to be ready for the clinic or when the laboratory is engaged to understand the reasons why a promising drug failed to achieve the expected level of efficacy in clinical trials. Much ...
The CryostaX® in vitro drug discovery and preclinical drug development test systems now include pooled Sprague-Dawley rat and CD-1 mouse hepatocytes.
If microchip systems that act like organs are ever going to really change preclinical drug development, its going to happen one experiment---and Big
Fig. 4. Mode of inhibition against PHD3 (left) where GSK1278863 IC50 values were plotted as a function of [α-KG]/Kmapp and fit to an equation for competitive inhibition. Determination of the dissociation half-life value (t1/2) for GSK1278863 from PHD3 by rapid dilution method (right). The yellow squares show the enzyme activity after dilution fit to an equation to determine the observed rate of recovery (kobs). Control reactions at 10x IC50 (black circles) and 0.1x IC50 (white squares) represent enzyme activity before dilution and after dilution if the compound was rapidly reversible. ...
Constitutive JAK2 activation in hematopoietic cells by the JAK2V617F mutation recapitulates myeloproliferative neoplasm (MPN) phenotypes in mice, establishing J
Membrane and protein traffic to the cell surface is mediated by partially redundant pathways that are difficult to perturb in ways that yield a strong phenotype. Such robustness is expected in a fine-tuned process, regulated by environmental cues, that is required for...
Caco-2 assays measure the ability of a drug to be absorbed from the gastrointestinal tract and thereby to evaluate whether the drug can be suitably dosed via an oral route. It also provides information regarding the ability of a compound to serve as a substrate for the P-glycoprotein (Pgp) efflux drug pump.. Caco-2 cells are intestinal epithelial tumor cells that form a polarized monolayer, a well-defined brush border on the apical surface and intercellular junctions when plated on a semipermeable membrane in a Transwell® dish.. ...
The data further verify the neuromuscular blocking properties of CW002, including rapid reversal by L-cysteine of 100% NMB under several circumstances. A notable lack of autonomic or circulatory effects provided added proof of safety and efficacy.
Citoxlab provides toxicity studies for new vaccine preclinical safety evaluation: immune response, reproductive toxicology, safety pharmacology, etc.
Certain anti-diabetic drugs increase this risk of bone fractures, particularly in postmenopausal women, severely limiting their treatment options.
Activating KRAS mutations are commonly seen in 40% to 50% of human CRC (13). Although the prognostic role of such mutations is controversial, it is evident that they are powerful positive predictors for resistance to treatment with anti-EGFR therapies, such as cetuximab or panitumumab (14, 15). Because of the central role for KRAS in EGFR and other receptor tyrosine kinase signaling pathways during CRC carcinogenesis (16), robust KRAS-specific treatments are desperately needed for effective CRC treatment. As such efforts have been widely unsuccessful to date (17), the development of novel therapeutic approaches for treatment of KRAS-mutant CRC is a critical unmet clinical need.. Despite the identification of many candidate drug compounds during preclinical discovery efforts, the subsequent rate of success through the clinical trial pipeline is abysmal (18). Traditional preclinical drug discovery platforms often rely on genetically undefined and highly passaged human tumor cell lines. The in ...
Enrich your medicines pipeline - Domainex provides a complete range of preclinical drug discovery services tailored to meet all your research needs
Preclinical pharmacokinetic models capable of predicting concentrations/exposure in vivo under different dosing schema can provide an invaluable tool for the rational design of clinical dosing protocols. The overall goals of the studies described herein were to design and evaluate the use of rational dosing protocols for vandetanib, docetaxel, and combinations of the two using pharmacokinetically directed dosing protocols that were reflective of exposures attainable in humans and that target antitumor and antiangiogenic responses. We utilized a PBPK model for docetaxel to develop dosing protocols that would allow us to examine the effects of standard docetaxel treatment versus a metronomic or antiangiogenic schedule of docetaxel. Pharmacokinetic data on vandetanib was used to determine a steady-state dose level that was reflective of human vandetanib exposure (32).. Preclinical testing is an integral part of the development of new therapeutics and new therapeutic strategies. With increasing ...
HOUSTON -- (March 15, 2010) -- The film Avatar isnt the only 3-D blockbuster making a splash this winter. A team of scientists from Houstons Texas Medical Center this week unveiled a new technique for growing 3-D cell cultures, a technological leap from the flat petri dish that could save millions of dollars in drug-testing costs. The research is reported in Nature Nanotechnology. The 3-D technique is easy enough for most labs to set up immediately. It uses magnetic forces to levitate cells while they divide and grow. Compared with cell cultures grown on flat surfaces, the 3-D cell cultures tend to form tissues that more closely resemble those inside the body. Theres a big push right now to find ways to grow cells in 3-D because the body is 3-D, and cultures that more closely resemble native tissue are expected to provide better results for preclinical drug tests, said study co-author Tom Killian, associate professor of physics at Rice. If you could improve the accuracy of early drug ...
Aberrant signaling through Fibroblast Growth Factor Receptors (FGFR) has been reported in multiple types of human cancers. FGFR4 signaling contributes to the development and progression of subsets of cancer: in approximately 10 percent of hepatocellular carcinoma (HCC), genetic amplification of FGF19, encoding an endocrine FGF ligand that activates FGFR4-KLB receptors, has been reported. In models with this alteration, FGF19-FGFR4 signaling is oncogenic and antagonism of the FGF19-FGFR4 axis has been shown to be efficacious suggesting that selective targeting of FGFR4 may be an effective strategy for malignancies with FGFR4 activation.. We describe the preclinical characterization of INCB062079 a potent and selective inhibitor of the FGFR4 kinase. In biochemical assays INCB062079 inhibited FGFR4 with low nM potency and exhibited at least 250-fold selectivity against other FGFR kinases and greater than 800-fold selectivity against a large kinase panel. This selectivity derives from the ability of ...
CBSET, a non-for-profit preclinical research institute dedicated to biomedical research, education and advancement of medical technologies, announced today that its scientists have published data and analyses (
A wide range of in vitro models are used in preclinical drug testing for the investigation of ADME-Tox properties of NCEs. The liver is the main organ with regards to ADME-Tox, wih over 500 different functions ...
OTTAWA, ON / ACCESSWIRE / May 6, 2020 / Tetra Bio-Pharma Inc. (Tetra or the Company) (TSXV:TBP)(OTCQB:TBPMF), a leader in cannabinoid-derived drug discovery and development, is pleased to announce that it has now completed the modifications to the nonclinical safety program of PPP003 to ensure the launch of a Phase 1 trial in healthy volunteers later this year and subsequently be able to initiate a Phase 2 trial in patients with COVID-19 immediately after.. The Company is not making any express or implied claims that its product has the ability to eliminate, cure or contain the Covid-19 (or SARS-2 Coronavirus) at this time. As with any new drug candidate, PPP003 has not been shown to be safe or effective in the prevention or treatment of inflammatory cytokine conditions. Dr. Melanie Kelly, Ph.D., Chief Scientific Officer, Tetra Bio-Pharma has read and approves of the scientific disclosure in this news release.. Tetras drug development program for PPP003 was adjusted to support a Clinical ...
Koen Dechering of TropIQ Health Sciences in the Netherlands is developing a high-throughput functional assay to identify new compounds that specifically block transmission of the malaria parasites to their vector hosts, which is a difficult stage to target, and to test candidate drugs. The assay incorporates luciferase- expressing parasites, which emit light as they develop in the mosquito midgut, along with barcoded chemical libraries. In Phase I, they tested several barcoding strategies and identified a bacterium that could be genetically modified to carry a unique barcode for identifying hit compounds selected in the screen. They also developed the luminescent reporter parasite to track transmission. In Phase II, they will further develop the assay for higher throughput, and screen compounds from the Tres Cantos Antimalarial Set and the MMV Validation, Malaria and Pathogen boxes. They will also use the assay to characterize the mechanisms of action of other candidate transmission-blocking ...
Posted By Carmen Drahl on Mar 21, 2010 , UPDATE April 2: If you read this coverage please tell us what you thought about it here or in the comments.. 1:26:15 PM: Im @ Moscone Ctr in San Fran. T minus half hour to unveiling of new drug candidate structures. #acsmedi #acs_sf. 1:37:35 PM: A hearty welcome to any readers of Totally Synthetic @Totsyn #acsmedi. 2:01:50 PM: 1st: Albert J. Robichaud-of Lundbeck-on Pfizers $PFE SAM-531, 5-HT6 antagonist for schizophrenia, Alzheimers #acsmedi #acs_sf. 2:02:53 PM: Alzheimers therapies today- palliative. Modulate eiether acetylcholine, glutamate #acsmedi #acs_sf. 2:04:58 PM: ~45 million ppl with ALzheimers worldwide- patients have probs w learning,memory, reasoning #acsmedi #acs_sf. 2:06:33 PM: 5HT6- 1 of 14 serotonin receptors- a G-protein coupled receptor #acsmedi #acs_sf. 2:07:00 PM: block 5HT6- boosts levels of glutamate, acetylcholine neurotransmission in brain areas assoc w/learning, memory #acsmedi #acs_sf. 2:09:37 PM: focus has been indole, ...
Although the scientific community continues to combat male bias in preclinical research, representation of women in late-phase clinical trials has improved markedly in recent years.21 The National Institutes of Health initiative to increase the use of female organisms and cells in preclinical research ensures that the scientific community as a whole will grow to fully address the health of both men and women. A major obstacle to the incorporation of female animals into studies, however, has been the belief that the rodent estrous cycle would render the study of these animals prohibitively expensive or difficult. Our study shows for the first time in a single large data set of physiological measurements that this belief is not accurate.. Our findings show that sex differences in CV among rats are small despite hormone fluctuations because of the estrous cycle. Moreover, for the majority of phenotypes, cohorts larger than typically used in preclinical research are required to detect the sex ...
A new drug candidate is more likely to be approved for use if it targets a gene known to be linked to the disease; a finding that can help pharmaceutical companies to focus their drug development efforts. Emily King and colleagues from AbbVie report these findings in a new study published Dec. 12 in PLOS Genetics.
Read how one laboratory created an automated drug discovery screening system to identify new drug candidates to fight bloodborne pathogens.
Psychiatric ailments have the bottom chance of success in scientific drug improvement. This presents not solely a problem to handle the unmet medical wants of sufferers, but in addition a hurdle for pharmaceutical and biotech business to proceed R&D on this illness space. Basic pharmacokinetic and pharmacodynamic rules present an understanding of the drug publicity, goal binding and pharmacological exercise on the goal website of motion for a brand new drug candidate. Collectively, these rules decide the probability of testing the mechanism of motion and enhancing the probability of candidate survival in Part 2 scientific improvement, due to this fact, theyre termed because the three pillars of survival. Human Part 1 pharmacokinetic and pharmacodynamic research present proof of the three pillars. Electroencephalogram (EEG) assessments and cognitive operate assessments in schizophrenia sufferers can present proof of pharmacology and be sure that a pharmacological lively routine might be ...
Cureline research team has adopted effective protocols for preparation of primary human cell lines from solid tumors, cancer blood, cancer bone marrow and normal tissues. The prepared primary cell cultures maintain their differential state and can be used as an in-vitro model system to study relevant disease changes and susceptibility to new drug candidates.
Together, we show that systematic pre-clinical evaluation and quantification of vaccine efficacy is vital for identification of the most potent whole organism anti-malaria vaccine strategy.. ...
<p>Kenyan scientists are revealing the potential for traditional herbal remedies to lead to new drug candidates to treat of herpes and malaria.</p>
ROCKVILLE, Md.--(BUSINESS WIRE)-- Rexahn Pharmaceuticals, Inc. (NYSE Amex: RNN), a clinical stage pharmaceutical company developing and commercializing potential best in class oncology and CNS
Are you looking for all the latest preclinical research news for across the life sciences. Find preclinical research news here at BioTechniques.
Confidence Beyond Compliance. Regulatory agencies offer sponsors guidance and regulations on what data is required for a products development, but there is not always clarity on when these studies need to be completed in respect to an investigational products stage of development. Furthermore, while ICH guidelines provide structure to global non-clinical strategies, there are often nuances to regional study design and execution that should be considered. While non-clinical efforts are most often associated with the objective of reaching first-in-man studies, non-clinical programs run the lifecycle of the drug development process. PharmaLex assists its clients by working closely with them to carefully balance what is required for each stage of development and registration while considering the variables of time and cost.. PharmaLex works with clients to design a customized program that best suits the clients needs. We place and monitor the program focusing on the following:. ...
Science & Biotech Career Center - Free Listing of Postdoc, Faculty Positions, Academic and Industrial Jobs
Tissue Organ Bath System is widely used in preclinical safety studies - considered as a valuable tool for the elucidation of the mechanism of action.
Following successful preclinical safety/ toxiciology studies, Patrys advanced PAT-SM6 into a first-in-human clinical trial in melanoma patients.
IITRI has more than 40 years of experience in the preclinical development of novel therapeutics and vaccines to protect against infectious diseases. Our services include efficacy and potency evaluations, toxicology and safety assessments, as well as analysis of human clinical trial samples.
ARC 64176 is the first of a new class of benzoylpyrrole calcium channel activators. It was undergoing preclinical trials with Aventis Pharma (formerly Hoechst
RNAis road from the clinic to the marketplace for drugs has been a bumpy one with the failure of some of the fields earliest candidates.
Noile-Immune signs its second high profile agreement, the latest with Adaptimmune to combine the companies technology in pre-clinical studies for the treatment of cancer.
In vivo imaging is at the heart of preclinical research into cancer biology and treatment, with advances in technology delivering tools that are ever more powerful, accurate and easy-to-use.
HCS Pharma is a biotechnological startup focused on in vitro preclinical research development with a specialisation in cellular imagery : High Content Analysis (HCA) and High Content Screening (HCS ...
HCS Pharma is a biotechnological startup focused on in vitro preclinical research development with a specialisation in cellular imagery : High Content Analysis (HCA) and High Content Screening (HCS ...
Laromustine is an experimental sulfonylhydrazine prodrug used in late-stage clinical studies against acute myeloid leukemia (AML) and glioblastoma multiforme (GBM). Despite initial promise for both indications, clinical trials for GBM have not been as successful as those for AML. To investigate methods for improving the effectiveness of laromustine in GBM and to learn more about the mechanism of action of laromustine, a chemical genetic screen will be conducted to identify agents that sensitize GBM cells to the anti-proliferative effects of laromustine. The library, which will include approximately 450 FDA-approved drugs, will be screened using a newly optimized high throughput assay based on the Click-iT EdU Microplate Assay kit (Molecular Probes). Optimization of the assay has required determining the proper cell seed density, drug concentration and incubation time, and fluorescent substrate concentration, among other variables. It was determined that low cell seed densities allow for maximal
On behalf of the National Center for Advancing Translational Sciences (NCATS), I invite BIO stakeholders to join us for our inaugural
We develop a flexible and computationally efficient approach for analyzing high-throughput chemical genetic screens. In such screens, a library of genetic mutants is phenotyped in a large number of stresses. Typically, interactions between genes and stresses are detected by grouping the mutants and …
XenoGesis Ltd. is a laboratory-based contract research organisation (CRO) specialised in preclinical drug metabolism & pharmacokinetics (DMPK), quantitative bioanalysis and expert interpretation.
9-(4-(18)F-Fluoro-3-[hydroxymethyl]butyl)guanine ((18)F-FHBG) is a sensitive and specific PET reporter probe for imaging the PET reporter genes, herpes simplex 1 thymidine kinase (HSV1-tk) and its mutant HSV1-sr39tk. (18)F-FHBG has suitable pharmacok
Definition of Indirect Liabilities in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is Indirect Liabilities? Meaning of Indirect Liabilities as a finance term. What does Indirect Liabilities mean in finance?
Definition of Secondary Liabilities in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is Secondary Liabilities? Meaning of Secondary Liabilities as a finance term. What does Secondary Liabilities mean in finance?
Due to the promising early results seen in patients with primary brain cancer, Reata has begun clinical trials of RTA 744 in patients who have other types of tumors (for example, lung or breast cancer) that have spread to the central nervous system (CNS). Reata Pharmaceuticals, Inc. is a biopharmaceutical company focused on developing novel treatments for cancer, inflammation, and neurodegenerative diseases. Reata is matching its clinical and preclinical drug development programs with a best-of-class drug discovery platform to identify small molecule chaperones that can induce proper folding of p53, SOD, and Tau, misfolded proteins that are involved in cancer and neurodegenerative disease.
Small-molecule microarrays composed of tens of thousands of distinct synthetic molecules, natural products, and their combinations/modifications provide a high-throughput platform for studying protein-ligand interactions. Immobilization of small molecule compounds on solid supports remains a challenge as widely varied small molecules generally lack unique chemical groups that readily react with singly or even multiply functionalized solid support. We explored two strategies for immobilizing small molecule compounds on epoxy-functionalized glass surface using primary-aminecontaining macromolecular scaffolds: bovine serum albumin (BSA) and amine-modified poly-vinyl alcohol (PVA). Small molecules with N-hydroxysuccinimide (NHS) groups were conjugated to BSA or amine-modified PVA. Small-molecule-BSA conjugates and small-molecule-PVA conjugates were subsequently immobilized on epoxy-functionalized glass slides through amine-epoxy reactions. Using an oblique-incidence reflectivity difference (OI-RD) ...
Cytotoxicity tests for high-throughput drug discovery.: Despite theoretical obstacles associated with performing cell-based assays in high-density formats (micr
Dr. Claire Le Pichon earned her B.A. degree from Cambridge University, U.K. and her Ph.D. in Biological Sciences from Columbia University in 2007 in the laboratory of Dr. Stuart Firestein, where her interest in neurodegenerative disease began while studying the function of the cellular prion protein PrPC. After her Ph.D., Dr. Le Pichon joined the Translational Neuroscience group at Genentech, where she worked on preclinical drug development for multiple neurodegenerative disease pipeline targets, using mouse models of disease. She was recruited as an Investigator to the NICHD in 2016. Her laboratory employs a multidisciplinary approach including mouse genetics, wide-scale imaging of whole brain tissue, next generation sequencing, and behavior to investigate the early events underlying the onset and progression of neurodegenerative disease. ...
TY - JOUR. T1 - Preclinical assessment of infant formula. AU - Lönnerdal, Bo. PY - 2012/6. Y1 - 2012/6. N2 - Infant formulas are the sole or predominant source of nutrition for many infants and are fed during a sensitive period of development and may therefore have short- and long-term consequences for infant health. Preclinical safety assessment therefore needs to include both short-term and long-term studies in animals. It is recommended that procedures are instituted by which experts may serve as independent scientists for companies developing novel products, without having their integrity compromised, and later serve the legislative institutions. A two-level assessment approach to determine the potential toxicity of a novel ingredient, its metabolites, and their effects in the matrix on developing organ systems has been suggested by IOM. This appears reasonable, as novel ingredients can be of different levels of concern. The use of modern methods in genomics and proteomics should be ...
AKT is frequently deregulated in cancer, making it an attractive anticancer drug target. CCT128930 is a novel ATP-competitive AKT inhibitor discovered using fragment-and structure-based approaches. It is a potent, advanced lead pyrrolopyrimidine compound exhibiting selectivity for AKT over PKA, achieved by targeting a single amino acid difference. CCT128930 exhibited marked antiproliferative activity and inhibited the phosphorylation of a range of AKT substrates in multiple tumor cell lines in vitro, consistent with AKT inhibition. CCT128930 caused a G(1) arrest in PTEN-null U87MG human glioblastoma cells, consistent with AKT pathway blockade. Pharmacokinetic studies established that potentially active concentrations of CCT128930 could be achieved in human tumor xenografts. Furthermore, CCT128930 also blocked the phosphorylation of several downstream AKT biomarkers in U87MG tumor xenografts, indicating AKT inhibition in vivo. Antitumor activity was observed with CCT128930 in U87MG and ...
Antibody drug conjugate (ADC) comprise of a monoclonal antibody and cytotoxic payload conjugated by a linker. The antibody is purposed to deliver the payload to the target located on the cancer cell. The payload is typically a highly potent small molecule, which should be released from the carrier antibody inside the tumour cell. The number of the released but differently conjugated small molecules is affected by the used conjugation method and strategy.
Read A simple high throughput assay to evaluate water consumption in the fruit fly, Scientific Reports on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
MNP001 is a newly synthesized 3-carbamyl-4-methylpyrrole analog with dual pharmacophores simultaneously to inhibit phosphodiesterase type 4 (PDE4) and to antagonize L-type calcium channels. The physicochemical properties of MNP001, including solubility, pKa, Log P, plasma protein binding and plasma/blood partitioning, were determined to support the pharmacokinetic characterization. The preclinical pharmacokinetic parameters were determined in an in vivo rat model and the metabolic pathways of MNP001 were characterized by incubating the compound in vitro in rat or human microsomes/supersomes cocktails. MNP001 was found to have a low solubility in simulated intestinal fluid but a high solubility in simulated gastric fluid. MNP001 is a highly lipophilic compound with a Log P value greater than 4. MNP001 was highly bound to the plasma protein and had an uneven partition between red blood cells and plasma. MNP001 exhibited a rapid absorption, broad distribution, slow systemic clearance and a low but
The PI3K pathway, which is commonly altered in numerous cancers (Liu et al., 2009a), has been identified as a promising target for the treatment of malignancies. Components of this signaling pathway, such as PI3K or mTOR, can be targeted by small molecules, and several inhibitors specific for one of these two kinases are being evaluated in patients (Engelman, 2009). Inhibitors of mTOR (mTORC1), referred to as rapalogs, have been approved for the treatment of cancers, and numerous dual PI3K/mTOR inhibitors are currently in clinical trials (Benjamin et al., 2011).. Preclinical pharmacokinetic studies provide key parameters during the discovery and the early stages of development of a compound. These parameters help to assess whether sufficient exposure can be achieved in further animal studies (efficacy and toxicology) and also are used to predict pharmacokinetic properties in humans. In addition, when integrated with efficacy data in PK-PD models, they can be used to estimate efficacious and ...
Rationale: Despite four decades of intense effort and substantial financial investment, the cardioprotection field has failed to deliver a single drug that effectively reduces myocardial infarct size in patients. A major reason is insufficient rigor and reproducibility in preclinical studies. Objective: To develop a multicenter randomized controlled trial (RCT)-like infrastructure to conduct rigorous and reproducible preclinical evaluation of cardioprotective therapies. Methods and Results: With NHLBI support, we established the Consortium for preclinicAl assESsment of cARdioprotective therapies (CAESAR), based on the principles of randomization, investigator blinding, a priori sample size determination and exclusion criteria, appropriate statistical analyses, and assessment of reproducibility. To validate CAESAR, we tested the ability of ischemic preconditioning (IPC) to reduce infarct size in three species (at two sites/species): mice (n=22-25/group), rabbits (n=11-12/group), and pigs ...
In early drug discovery (e.g., in fragment screening), recognition of stereoisomeric structures is valuable and guides medicinal chemists to focus only on useful configurations. In this work, we concurrently screened mixtures of stereoisomers and estimated their affinities to a protein target (thrombin) using weak affinity chromatography-mass spectrometry (WAC-MS). Affinity determinations by WAC showed that minor changes in stereoisomeric configuration could have a major impact on affinity. The ability of WAC-MS to provide instant information about stereoselectivity and binding affinities directly from analyte mixtures is a great advantage in fragment library screening and drug lead development.
Drug Discovery Today is a review journal, published as monthly 12 double issues. The journal covers the whole of the preclinical drug discovery process, from target identification and validation, through hit identification, lead identification and optimisation, though to candidate selection. The reviews are at the cutting edge of the science underpinning drug discovery, written by experts in their respective fields and cover all aspects of drug discovery from state-of-the-art genomic and proteomic approaches to target identification, through the most innovative computational approaches drug design, the science driving medicinal chemistry and the translation of these sciences to therapies
Drug Discovery Today is a review journal, published as monthly 12 double issues. The journal covers the whole of the preclinical drug discovery process, from target identification and validation, through hit identification, lead identification and optimisation, though to candidate selection. The reviews are at the cutting edge of the science underpinning drug discovery, written by experts in their respective fields and cover all aspects of drug discovery from state-of-the-art genomic and proteomic approaches to target identification, through the most innovative computational approaches drug design, the science driving medicinal chemistry and the translation of these sciences to therapies
Technology Networks is an internationally recognised publisher that provides access to the latest scientific news, products, research, videos and posters.
Downloadable! This paper studies the interdependence of households? financial assets and liabilities in European countries. Most studies treat household liabilities as negative assets and relate households? decisions to their net wealth. However, the components of net wealth, i.e. financial liabilities, financial assets and real assets are very heterogeneous across households. The assumption of similar consumption behaviour among households with the same net wealth but different wealth components is implausible. This paper raises another question, namely whether households consider their indebtedness when they make decisions about their financial assets. The implication of household indebtedness for household behaviour is an important topic as household debt volumes have increased markedly in developed countries over the last three decades. There is a long list of research about household borrowing and the financial vulnerability of indebted households, but there has been less discussion about whether
Lundbeck divests preclinical research programs Two programs outside Lundbecks areas of focus are transferred to MindImmune Therapeutics, Inc. H. Lundbeck A/S (Lundbeck) further focuses its preclinical research pipeline with the divestment of two research programs to biotech company MindImmune Therapeutics, Inc. (MindImmune). In exchange for the programs, Lundbeck receives an equity interest in MindImmune as well as milestone payments and royalties according to the progression of the programs. The agreement follows Lundbecks strategy of focusing its efforts within four disease areas; depression, schizophrenia, Alzheimers disease and Parkinsons disease, for which the programs are not relevant. Per its strategy Lundbeck itself has therefore not prioritized further development of the programs, but the agreement ensures that these potential new treatments will now be brought forward. There will be no costs for Lundbeck associated with the future development of the programs. We focus on ...
Comparative Biosciences, Inc. provides expert scientific resources and quality service to all sectors of the biomedical and biopharmaceutical community. We offer extensive experience in GLP and non-GLP preclinical toxicology, efficacy, pharmacology, pharmacokinetics-pharmacodynamics, histopathology and safety studies on all laboratory species.
Virtual drug screening is one of the most widely used approaches for finding new drugs candidates. The process consists in selecting one or more chemical compounds with the highest binding free energy to target proteins. Given that the empirical space of chemical compounds is extremely large and estimated to has over 50 millions of them, finding the most effective drug becomes computationally challenging. Furthermore, the vast majority of proteins still lack the experimentally obtained 3D structures required for most of the molecular computer tools available, making it impossible to calculate their binding free energies with chemical compounds. In view of this, the aim of our study is to asses the effectiveness of the Autodock Vina tool in a large environments with unstructured proteins, those without defined 3D structure. The ultimate goal is to enable a fast and efficient virtual drug screening in such an environments, and to apply it for discovery of a new drug candidates.. ...
此為系統發信請勿直接回覆。若您希望取消訂閱本公司電子報,請按這裡寄送退訂訊息給我們,謝謝 ...
The aim of the present study is to test the effect of a 15-day treatment with donepezil on a mixed battery associating cognitive assessment, imaging and neurophysiological tests in healthy volunteers.. This multicenter, randomized, placebo-controlled, cross-over study is double-blind controlled and is conducted in 3 centers located in France (Lille, Marseille and Toulouse).. 18-30 years old, healthy volunteers, without any neurological or psychiatric impairment, will complete 2 test sessions in a randomized order: one with a 15-day treatment with donepezil, the other with placebo, and will be submitted to a mixed battery during the 14th and 15th day of the treatment. The primary outcome of the study will be based on cognitive assessment, imaging parameters and neurophysiological parameters. ...
Eventbrite - Michigan Association of OWI Attorneys & State Bar of Michigan Marijuana Law Section presents Drug Evaluation and Classification Course - Friday, May 8, 2020 | Saturday, May 9, 2020 at The James B. Henry Center for Executive Development, Lansing, MI. Find event and ticket information.
In the absence of an efficient vaccine, prevention of HIV transmission remains the primary and economically feasible infection prevention method available to da...
Following publication of the original article [1], the authors found an error in Figure 3. The middle panel of Figure 3a was inadvertently duplicated.
Atomwise announced the launch of a ten billion compound AI-powered virtual drug screening initiative, the 10-to-the-10 program, in collaboration with Enamine, the worlds largest chemical supplier. The initiative aims to dramatically increase the discovery of safer small molecule drugs to treat pediatric cancers.. Atomwise will use its patented AI virtual screening technology to evaluate the binding of billions of drug-like molecules to cancer target proteins, and Enamine will provide support and access to a virtual library of ten billion small molecule compounds. The research will be directed by the needs of innovators in cancer research at leading universities.. Cancer is diagnosed in more than 15,000 children and adolescents each year. Many cancers do not have effective treatments and for those that do, it is estimated that 80% have serious adverse effects that impact long-term health. Therefore, new oncology drugs are needed. The 10-to-the-10 program will search for novel drug candidates by ...
In 2009, the same development team created Adam, a robot scientist that became the first machine to independently discover new scientific knowledge. They used the knowledge from that experiment to create Eve with the purpose of speeding up the drug discovery process and make it more economical. In the published study, the researchers discuss describe how the robot is able to identify promising new drug candidates for malaria and other neglected tropical diseases, such as African sleeping sickness and Chagas disease.. Neglected tropical diseases are a scourge of humanity, infecting hundreds of millions of people, and killing millions of people every year, said Steve Oliver, a professor from the Cambridge Systems Biology Centre and the Department of Biochemistry at the University of Cambridge. We know what causes these diseases and that we can, in theory, attack the parasites that cause them using small molecule drugs. But the cost and speed of drug discovery and the economic return make them ...
REGENXBIO total liabilities from 2014 to 2020. Total liabilities can be defined as the total value of all possible claims against the corporation.
Most preclinical studies that aim to prove the antistroke efficacy of candidate drugs are performed in experimental settings bearing little-if any-resemblance to clinical reality, which is a possible reason for several neuroprotective drug failures (36,37). Potential causes of this lack of success include use of preclinical drug administration paradigms not achievable at the clinic level (e.g., drug administration before or very shortly after stroke, intracerebroventricular injections, and too-high doses of the candidate drugs (38)), efficacy experiments performed using animal models that lack common comorbidities of stroke patients, such as diabetes and hypertension (36), and finally, nearly all rodent stroke studies are performed in young animals, whereas most stroke patients are elderly (39).. Our goal in the current study was to determine the potential antistroke efficacy of a DPP-4 inhibitor therapy by mimicking the likely clinical scenario of an obese type 2 diabetic patient receiving this ...
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
PRECLINICAL PHARMACOLOGICAL STUDIES OF ANTITUMOR AND ANTI-HIV AGENTS NIH GUIDE, Volume 23, Number 3, January 21, 1994 RFP AVAILABLE: NCI-CM-57199-12 P.T. 34 Keywords: Pharmacology Chemotherapeutic Agents National Cancer Institute The Developmental Therapeutics Program (DTP), Division of Cancer Treatment, is soliciting organizations having the necessary experience, scientific and technical personnel, and facilities to conduct a series of preclinical pharmacokinetic and other pharmacology studies in non-disease bearing animals on agents having demonstrated antitumor or anti-HIV activity and considered by DCT to merit further development. The studies to be performed will include: the development of methodology for the quantitative measurement of test agents and/or metabolites in animal body fluids and tissues; stability studies of test agents in biological fluids; plasma protein binding determinations; characterization of in vivo plasma concentration-time profiles and calculation of relevant ...
Zhang L, Balan G, Barreiro G, Boscoe BP, Chenard LK, Cianfrogna J, Claffey MM, Chen L, Coffman KJ, Drozda SE, Dunetz JR, Fonseca KR, Galatsis P, Grimwood S, Lazzaro JT, Mancuso JY, Miller EL, Reese MR, Rogers BN, Sakurada I, Skaddan M, Smith DL, Stepan AF, Trapa P, Tuttle JB, Verhoest PR, Walker DP, Wright AS, Zaleska MM, Zasadny K, Shaffer CL. Discovery and preclinical characterization of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo-[3,4-b]pyrazine (PF470): a highly potent, selective, and efficacious metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator. J Med Chem. 2014 Feb 13; 57(3):861-77 ...
Next, an unlabeled compound was analyzed using the kinetic probe competition assay. The reaction contained fluorescent tracer 178 and the indicated concentrations of staurosporine, an unlabelled ABL-binder. The reaction was started by adding Tb-labelled ABL resulting in a signal increase for the trace without competitor (Fig. 3, grey). In contrast, the signal in presence of the competitor is lower the higher its concentration, and the initial signal increase is followed by a decrease in signal over time. The latter indicates that due to slower binding kinetics the competitor equilibrates more slowly than the tracer. ...
Herein are a collection of studies that build on our existing knowledge of estrogen actions in the brain. We extend the efforts of current neuroprotective strategies by demonstrating that estrogenic molecules promote cell survival mechanisms governed by neuronal mitochondria. Estrogen (E2, 17beta-estradiol) protects neurons from a series of age-related risk factors for developing Alzheimer s disease (AD) supported by basic science, clinical, and epidemiological data. However, there exists a window of opportunity for E2 as a preventive therapy and our findings are not intended for hopeful treatments of pre-existing pathologies but rather to support the proposed healthy-cell bias therapeutic approach (Brinton 2005). Our preclinical pharmacology research work covers biochemistry, molecular biology and cell imaging of rodent brain. Controlled in vitro and in vivo studies are organized under four specific aims that test our hypotheses in brain tissues with a focus on the hippocampus and cortex ...
Gliobastoma multiforme (GBM) is an aggressive malignant form of brain tumour for which effective therapies are limited. Genetically engineered mouse models (GEMMs) harbouring mutations in components of the main signalling pathways that are altered in human GBM - including the receptor tyrosine kinase (RTK)-RAS- phosphoinositide-3-kinase (PI3K) pathway - are available. However, these GEMMs display a long latency to tumorigenesis and advanced tumour heterogeneity, which represents a challenge in preclinical drug testing. In this study, Zoë Weaver Ohler and colleagues developed an orthotopic and tractable mouse model of GBM by transplanting brain tumour cells derived from GBM-GEMMs into the brain (orthotopically) of syngeneic mice (non-transgenic wild-type mice with identical genetic backgrounds and intact immune systems). This model develops GBM with features of the human disease, including high vascularisation and aggressive invasion of surrounding tissues, and thus was used to test the effects ...
Other articles where Current liability is discussed: accounting: The balance sheet: …liabilities are similarly divided into current liabilities and noncurrent liabilities. Most amounts payable to the companys suppliers (accounts payable), to employees (wages payable), or to governments (taxes payable) are included among the current liabilities. Noncurrent liabilities consist mainly of amounts payable to holders of the companys long-term bonds and such…
[email protected] Course Description. This three-credit course is intended to help Master of Science students in the Preclinical Pharmacology Track of the existing MBS Program understand the skills required to integrate pharmacotherapeutic and pathophysiologic concepts through use of clinical case studies. The course will be conducted in an interactive small group format with no more than 15 students per class. The course will consist of seven three-hour sessions, in which clinical cases will be presented and discussed. Prior to each class session, students will be provided with the descriptions of the cases assigned for that session as well as specific questions relating to each assigned case that will be discussed in class. Using reliable information sources (including two free online textbooks), students will be expected to formulate responses to the case questions in advance of each class session, and to engage in interactive discussions of the questions during the class period. ...
Object. Determining the efficacy of a drug used in experimental traumatic brain injury (TBI) requires the use of one or more outcome measures such as decreased mortality or fewer neurological and neuropsychological deficits. Unfortunately, outcomes in these test batteries have a fairly large variability, requiring relatively large sample sizes, and administration of the tests themselves is also very time consuming. The authors previously demonstrated that experimental TBI and human TBI induce mitochondrial dysfunction. Because mitochondrial dysfunction is easy to assess compared with neurobehavioral endpoints, it might prove useful as an outcome measure to establish therapeutic time windows and dose-response curves in preclinical drug testing. This idea was tested in a model of TBI in rats.. Methods. Animals treated with the selective N-type voltage-sensitive calcium channel blocker Ziconotide (also known as SNX-111 and CI-1009) after cortical impact displayed significant improvement in brain ...
|p||em|Reaxys Medicinal Chemistry enables scientists to explore new drug candidates through a comprehensive database with new search features, refined user-interface and integration with Reaxys|/em||/p|
August 1987). "Preclinical safety evaluation of the benzodiazepine quazepam". Arzneimittelforschung. 37 (8): 906-13. PMID ... Two types of drug misuse can occur, either recreational misuse where the drug is taken to achieve a high, or when the drug is ... "FDA expands Boxed Warning to improve safe use of benzodiazepine drug". U.S. Food and Drug Administration (FDA). 23 September ... This makes quazepam unique in the benzodiazepine family of drugs. Quazepam is a drug with the potential for misuse. ...
O'Neill, AJ; Chopra, I (2004). "Preclinical evaluation of novel antibacterial agents by microbiological and molecular ... Riegel, Ralph (2008-08-08). "Man died after rare medical reaction to cholesterol drug". Irish Independent. Drug Safety Update ... A Newly Identified Drug-Drug Interaction". Clinical Infectious Diseases. 63 (12): 1599-1604. doi:10.1093/cid/ciw665. PMID ... The drug is licensed for use as its sodium salt sodium fusidate, and it is approved for use under prescription in South Korea, ...
As such, MICs are usually the starting point for larger pre-clinical evaluations of novel antimicrobial agents. The purpose of ... When the MBC is much higher than the MIC, drug toxicity makes taking the MBC of the drug detrimental to patient. Antimicrobial ... ISBN 1-55581-255-4. O'Neill AJ, Chopra I (August 2004). "Preclinical evaluation of novel antibacterial agents by ... The first step in drug discovery is often the screening of a library drug candidate for MICs against bacteria of interest. ...
Han C, Davis CB, Wang B (6 January 2010). Evaluation of Drug Candidates for Preclinical Development: Pharmacokinetics, ... "Drug Product Database Online Query". 2012-04-25. "Drug Product Database Online Query". 2012-04-25. "Drug Product Database ... ISBN 978-3-13-179275-4. Muller (19 June 1998). European Drug Index: European Drug Registrations, Fourth Edition. CRC Press. pp ... The drug was administered to pregnant rats and its effects on the rat fetuses were studied. To the surprise of the researchers ...
7]. FDA U.S. Department of Health and Human Services Food and Drug Administration - Center for Drug Evaluation and Research ( ... 2]. ICH S6(R1): Preclinical safety evaluation of biotechnology-derived pharmaceuticals. [3]. ICH S9: Nonclinical evaluation for ... 8]. FDA U.S. Department of Health and Human Services Food and Drug Administration - Center for Drug Evaluation and Research ( ... If these evaluation efforts succeed, CiPA will become a Safety Pharmacology screening tool for drug research and development ...
"Risk Evaluation and Mitigation Strategy (REMS) Under Review for CellCept and Myfortic". U.S. Food and Drug Administration. ... Taylor, DO; Ensley, RD; Olsen, SL; Dunn, D; Renlund, DG (1994). "Mycophenolate mofetil (RS-61443): preclinical, clinical, and ... it would become an immunosuppressive drug for autoimmune diseases and organ transplantation. In 1981 he decided to go for drug ... After successful clinical trials, the compound was approved for use in kidney transplant by the US Food and Drug Administration ...
"Risk Evaluation and Mitigation Strategy (REMS) Under Review for CellCept and Myfortic". U.S. Food and Drug Administration. ... Taylor DO, Ensley RD, Olsen SL, Dunn D, Renlund DG (1994). "Mycophenolate mofetil (RS-61443): preclinical, clinical, and three- ... "Mycophenolic acid". Drug Information Portal. U.S. National Library of Medicine. "Mycophenolate mofetil". Drug Information ... Common adverse drug reactions (≥1% of people) include diarrhea, nausea, vomiting, joint pain; infections, leukopenia, or anemia ... Kusiak V (2013-02-13). "NDA Approval" (PDF). U.S. Food and Drug Administration. Center for Drug Evaluation and ... Preclinical trials were performed in ovariectomized rats to model menopause. Oral ospemifene was compared with raloxifene ( ... McCall JL, DeGregorio MW (June 2010). "Pharmacologic evaluation of ospemifene". Expert Opin Drug Metab Toxicol. 6 (6): 773-9. ... A New Drug Application (NDA) was submitted to the FDA on April 26, 2012. Amendments to the NDA were submitted in June, July, ...
2007). "Preclinical antitumor activity of a novel folate-targeted dual drug conjugate". Mol. Pharm. 4 (5): 659-67. doi:10.1021/ ... May 2007). "Preclinical evaluation of EC145, a folate-vinca alkaloid conjugate". Cancer Res. 67 (9): 4434-42. doi:10.1158/0008- ... Reddy JA, Xu LC, Parker N, Vetzel M, Leamon CP (May 2004). "Preclinical evaluation of (99m)Tc-EC20 for imaging folate receptor- ... Targeted drug therapy is advantageous because it deposits the drug at the specific location where it can be most useful in ...
Based on this data, alogliptin was chosen for preclinical evaluation. In January 2007 alogliptin was undergoing the phase III ... In recent years, new drugs have been developed, based on continuing research into the mechanism of insulin production and ... It is a well-known DPP-4 inhibitor developed by GlaxoSmithKline (GSK). Biological evaluations have shown that the S- ... In 1999, Merck started a drug development program on DPP-4 inhibitors. When they started internal screening and medicinal ...
Preclinical pharmacology and toxicity testing : Preclinical safety testing of antibody is designed to identify possible ... Heterodimeric antibodies have a greater range in shapes they can take and the drugs that are attached to the arms don't have to ... evaluation of the potential clinical effects ... Preclinical studies[edit]. Example of tissue cross-reactivity ... allow for greater flexibility and new formats for attaching a variety of drugs to the antibody arms. One of the general formats ...
"Preclinical evaluation of melanin-concentrating hormone receptor 1 antagonism for the treatment of obesity and depression". The ... CNS Drug Reviews. 11 (4): 341-52. doi:10.1111/j.1527-3458.2005.tb00052.x. PMC 6741758. PMID 16614734. Gehlert DR, Rasmussen K, ... "Synthesis and biological evaluation in vitro of a selective, high potency peptide agonist of human melanin-concentrating ... CNS Drugs. 20 (10): 801-11. doi:10.2165/00023210-200620100-00002. PMID 16999451. Hervieu GJ (Apr 2006). "Further insights into ...
May 2009). "Preclinical evaluation of melanin-concentrating hormone receptor 1 antagonism for the treatment of obesity and ... GW-803430 (GW-3430) is a drug used in scientific research and is a selective non-peptide antagonist at the melanin ... Chaki S, Kanuma K (2007). "Neuropeptide receptors: Novel therapeutic targets for depression and anxiety disorders". Drugs of ...
"Synthesis and preclinical evaluation of QS-21 variants leading to simplified vaccine adjuvants and mechanistic probes". J Am ... The crude drug (Quillajae cortex) is imported from Peru and Chile. The extract contains water-soluble triterpene glycosides, ... 2004). Herbal Drugs and Phytopharmaceuticals: A Handbook for Practice on a Scientific Basis. Medpharm Publishers. p. 492. ISBN ... QS-21 has undergone clinical evaluation as an additive for various trial vaccines, including those for HIV, malaria and cancer ...
... has several drugs in preclinical development. A current target is Heat Shock Protein 90 (HSP90). HSP90 is key in ... LEO Pharma sold TopoTarget the license to its preclinical HDAC inhibitor, which is also undergoing evaluation as a treatment ... Currently TopoTarget has nine drugs in clinical development, as well as an extensive portfolio of small molecule drug ... APO866, a drug that inhibits the growth of human tumors, is a potent and specific inhibitor of a key enzyme that is involved in ...
"A summary of preclinical topical microbicide vaginal safety and chlamydial efficacy evaluations in a pigtailed macaque model". ... "AIDSinfo - HIV/AIDS Drug Information - PRO 2000". 2011. Archived from the original on October 17, 2011. ... Endo Pharmaceuticals manufactures the drug. Animal testing studies done on macaques have shown that PRO 2000 is effective in ...
"Preclinical antitumor evaluation of bis-acetato-ammine-dichloro-cyclohexylamine platinum(IV): an orally active platinum drug" ( ... Once the molecule makes it to the bloodstream the drug loses its acetate groups. At this point the drug is structurally similar ... The drug has also been used in the treatment of lung and ovarian cancers. The proposed mode of action is that the compound ... Since the drug is now structurally similar to cisplatin its mechanism of action is also very similar. The chlorine atoms are ...
"Positive Preclinical Results for Lung Cancer Drug Announced at Annual Meeting of Cancer Research - Lung Disease News". Lung ... Research, Center for Drug Evaluation and (2020-05-26). "FDA approves brigatinib for ALK-positive metastatic NSCLC". FDA. "BRIEF ... "Ariad CEO on Developing New Drugs". Fox Business. 2011-07-15. Retrieved 2017-11-10. "Ariad CEO on the Three Drugs in the ... ARIAD's plan was to develop drugs that would interfere with communication signals within cells, rather than on the cell surface ...
The drug has reportedly been in pre-clinical development for all medical indications since 2008. Palatin has stated that "We ... are focusing development efforts on bremelanotide for [female sexual dysfunction], but are continuing evaluation of PL-6983." ... List of investigational sexual dysfunction drugs Melanocortin 4 receptor § Agonists Natasha Mitchner (2009). Hypoactive Sexual ...
The company has at least 8,000 viable human tumors that can be used for the evaluation of drugs used in oncology studies. ... Fassbender, Melissa (4 January 2018). "JSR: CrownBio purchase to support 'major opportunity' in preclinical space". Outsourcing ... The company keeps a library of cancer models used for drug-testing that precedes clinical trials. The company applied for ... CrownBio's signature products include a library of xenograft models used for drug testing and contract research services for ...
... drug candidates and biological dose assessment technologies are developed up to and through preclinical testing and evaluation ... The program seeks to develop prophylactic and therapeutic drugs, such as Ex-Rad, that prevent and treat radiation injuries and ...
3,6-Disubstituted triazolo-thiadiazole compounds are under preclinical evaluation (including animal models) as antivirulence ... Therefore, in October 2016 the US Food and Drug Administration (FDA) and in July 2018 the Italian Drug Agency (AIFA) approved ... Dickey, S.W, Cheung, G.Y.C, Otto, M. Different drugs for bad bugs: antivirulence strategies in the age of antibiotic resistance ... Cascioferro, S., Totsika, M., & Schillaci, D. (2014). Sortase A: An ideal target for anti-virulence drug development. Microbial ...
4. Design, synthesis, and preclinical evaluation of 7-aryltriazolo[4,5-d]pyrimidines". Journal of Medicinal Chemistry. 52 (1): ... Drug Discovery. 15 (9): 605-19. doi:10.1038/nrd.2016.109. PMID 27417849. Hubbard RE, Murray JB (1 January 2011). "Experiences ... Erlanson DA, Fesik SW, Hubbard RE, Jahnke W, Jhoti H (September 2016). "Twenty years on: the impact of fragments on drug ... Vernalis Research has delivered a number of drug candidates into clinical development, some of which remained as part of the ...
Since 2001, the Center for Drug Evaluation and Research has averaged 22.9 approvals a year. This approval comes only after ... This process generally involves submission of an Investigational New Drug filing with sufficient pre-clinical data to support ... Drug discovery is the process by which potential drugs are discovered or designed. In the past, most drugs have been discovered ... Marketing of prescription drugs in the US is regulated by the federal Prescription Drug Marketing Act of 1987. The book Bad ...
... and preclinical evaluation of antibacterial drug candidates. Her research includes seminal contributions in the understanding ... Expert Opin Drug Discov. 2008;3(5):487‐500. doi:10.1517/17460441.3.5.487 Young K, Jayasuriya H, Ondeyka JG, et al. Discovery of ... Expert Opin Drug Discov. 2013 Feb;8(2):143-56. doi: 10.1517/17460441.2013.743991. Epub 2012 Dec 19. Silver LL. Are natural ... Silver, L.; Chandler, M.; Tour, E. B. de la; Caro, L. (1977-09-01). "Origin and direction of replication of the drug resistance ...
Food and Drug Administration issued recommendations for the establishment of a cardiac safety profile during pre-clinical drug ... The nonclinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human ... both of which can result in decreased channel function and drug-induced (acquired) long QT syndrome. Among the drugs that can ... Preclinical hERG studies should be accomplished in GLP environment. The hERG gene was first named and described in a paper by ...
... 's research is based on a model that includes preclinical evaluation of new and FDA-approved drugs in ... The drugs are tested in clinical trials involving both pediatric and adult cancer centers from within the CERN network. The ... This project serves as a testing ground for new diagnostic and drug discoveries made in Projects Two and Three. Tumor Profiling ... The project also provides insights into the design of CERN's future clinical trials, and all CERN trials include evaluation of ...
A vaccine candidate drug is first identified through preclinical evaluations that could involve high throughput screening and ... The preclinical stages are necessary to determine approximate dose ranges and proper drug formulations (i.e., tablet, injection ... are necessary components of the preclinical stage. Other drug trials focus on the pharmacodynamics and pharmacokinetics; ... The drug is introduced into a small cohort of healthy volunteers. Vaccine escalation studies aim to minimize chances of serious ...
... that the use of epigenetic modifications as therapeutic targets warrant extensive preclinical as well as clinical evaluation ... This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other drugs, and tendency to ... They control gene expression including virulence genes in pathogens and are viewed as new targets in the fight against drug- ... These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken ... In ...
This work involves molecular diagnostics, drug and vaccine efficacy evaluations, drug and vaccine safety evaluations, and ... Mechanistic studies are performed at the cell, biochemical, and molecular levels, and preclinical drug discovery and ... The various research efforts in the foregoing divisions supports Drug Discovery Division with Investigational New Drug (IND) ... safety evaluations, and drug discovery and development. In 2006, IITRI formed Technology Research, Inc. (TRI), as a wholly ...
Androgen receptor antagonists: drugs that bind directly to and block the AR.[57][58] These drugs include the steroidal ... IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; World Health Organization; International Agency for ... "Preclinical characterization of a novel diphenyl benzamide selective ERα agonist for hormone therapy in prostate cancer". ... Drug class. Bicalutamide, a nonsteroidal antiandrogen and the most widely used androgen receptor antagonist in the treatment of ...
Drug design. Steps in design. *Drug discovery. *Hit to lead. *Drug development *Pre-clinical ... binding assay and pharmacological evaluation of 1,2,4-triazolo[1,5-a]pyrimidinone and 3-amino-1,2,4-triazole derivatives". ... Gringauz A (1997). Medicinal Chemistry How drugs act and why. United States of America: WILEY-VCH. pp. 578-579. ISBN 0-471- ... Gringauz A (1997). Medicinal Chemistry How drugs act and why. United States of America: Wiley-VCH. pp. 572-574. ISBN 0-471- ...
A number of in vitro and in vivo models lend themselves to preclinical evaluation of novel pulmonary therapies. In vitro, ... Drugs that reduce the inflammatory response, promote healing of tissues, and prevent the onset of pulmonary edema or secondary ... Several drugs that have been approved by the FDA for other indications hold promise for treating chemically induced pulmonary ... Other promising drugs in earlier stages of development act at various steps in the complex molecular pathways underlying ...
Additionally, in most preclinical studies the SOD1 mice were given the drug during the presymptomatic stage; this makes the ... Watanabe Y, Watanabe T (October 2017). "Meta-analytic evaluation of the association between head injury and risk of amyotrophic ... Drugs tested and not shown to be effective in clinical trials in humans include antiviral drugs, anti-excitotoxic drugs, growth ... "FDA approves drug to treat ALS". U.S. Food and Drug Administration. 5 May 2017. Archived from the original on 8 May 2017.. ...
June 2001). "Preclinical evaluation of CHF3381 as a novel antiepileptic agent". Neuropharmacology. 40 (7): 866-78. doi:10.1016/ ... "CHF 3381". Drugs in R&D. 5 (1): 28-30. 2004. doi:10.2165/00126839-200405010-00005. PMID 14725488.. ... Indantadol (CHF-3381, V-3381) is a drug which was formerly being investigated as an anticonvulsant and neuroprotective and is ... September 2001). "Anticonvulsant preclinical profile of CHF 3381: dopaminergic and glutamatergic mechanisms". Pharmacology ...
An evaluation of peak inspiratory pressure, tidal volume, and ventilatory frequency during ventilation with a neonatal self- ... however the pre-clinical experiments associated with these findings involved delivery of inspiratory volumes in excess of ...
Begley, C. G.; Ellis, L. M. (2012). "Drug development: Raise standards for preclinical cancer research". Nature. 483 (7391): ... Subcommittee E11.20 on Test Method Evaluation and Quality Control (2014), Standard Practice for Use of the Terms Precision and ... Prinz, F.; Schlange, T.; Asadullah, K. (2011). "Believe it or not: How much can we rely on published data on potential drug ... A Phase I discovery will be followed by Phase II reproductions as a drug develops towards commercial production. In recent ...
... pre-clinical development, and clinical translation. SRI has helped move more than 100 drugs into clinical trials. [117][118]. ... SRI education researchers conducted the first national evaluation of the growing U.S. charter schools movement. For the World ... In medicine and chemistry, SRI developed dry-powder drugs,[86] laser photocoagulation (a treatment for some eye maladies),[87] ... "SRI International Licenses Drug Formulation Process to Dura Pharmaceuticals". SRI International. 1997-07-01. Archived from the ...
"FDA approves new drug for advanced prostate cancer" (Press release). Food and Drug Administration. 15 May 2013. Archived from ... Pre-clinical. Arachidonate 5-lipoxygenase has been identified as playing a significant role in the survival of prostate cancer ... A study based on the 1998 Patient Care Evaluation in the US found that about a third of patients diagnosed with prostate cancer ... Seruga B, Ocana A, Tannock IF (January 2011). "Drug resistance in metastatic castration-resistant prostate cancer". Nature ...
Preclinical evaluation of CP868,596, a novel PDGFR Inhibitor for treatment of glioblastoma". Cancer Research. 71 (8 Supplement ... "Crenolanib Inhibits the Drug-Resistant PDGFRA D842V Mutation Associated with Imatinib-Resistant Gastrointestinal Stromal Tumors ... Evaluation of the antitumor activity of crenolanib in a genetically engineered BSG DIPG mouse model showed that it is highly ...
There is also concern with respect to the numerous well-established interactions of herbs and drugs.[41] In consultation with a ... In a 2010 global survey of the most common 1000 plant-derived compounds, 156 had clinical trials published.[18] Preclinical ... Cravotto G, Boffa L, Genzini L, Garella D (February 2010). "Phytotherapeutics: an evaluation of the potential of 1000 plants". ... In the United States, herbal remedies are regulated dietary supplements by the Food and Drug Administration (FDA) under current ...
The first four years of training are considered preclinical, and the final two years are clinical. In 2006, there were 79 ... doi:10.1111/j.1523-536X.1989.tb00867.x. Suzuki, Ritsuko; Horiuchi, Shigeko; Ohtsu, Hiroshi (September 2010). "Evaluation of the ... Drug Development Research, special issue: A Hot Topic. An update on radiological countermeasures following the Fukushima ...
Research, Center for Drug Evaluation and. "Drug Safety and Availability - FDA Drug Safety Communication: Safety Review Update ... Although useful in the treatment of ADHD, stimulants are controlled II substances with a history of preclinical and human ... Patient-Focused Drug Development Initiative" (PDF). Center for Drug Evaluation and Research (CDER) U.S. Food and Drug ... " Archived from the original on 14 August 2013.. *^ "World Drug Report 2015" (PDF). Archived (PDF) from the ...
"Preclinical evaluation of a mercaptobenzamide and its prodrug for NCp7-targeted inhibition of human immunodeficiency virus". ... Zinc ejectors were patented in 2008 and some have entered Phase I/II trials as a HIV drug. The HIV-1 nucleocapsid protein 7 ( ... These processes play critical roles in the replication of HIV-1 thus making NCp7 a prime target for drugs seeking to contravene ... The mercaptobenzamide and its corresponding prodrug yielded additivity to synergy when combined with known HIV drugs. Moreover ...
Antibody-drug conjugates[edit]. Antibody-drug conjugates (ADCs) comprise an antibody, drug and a linker between them. The ... Sekhon SS, Roy V (May 2006). "Thrombocytopenia in adults: A practical approach to evaluation and management". Southern Medical ... "Electrochemotherapy: aspects of preclinical development and early clinical experience". Annals of Surgery. 245 (3): 469-479. ... drug-to-drug interactions, genetics, and obesity, which has a major impact on the actual concentration of the drug in the ...
Fink MP, Warren HS (October 2014). "Strategies to improve drug development for sepsis". Nature Reviews Drug Discovery. 13 (10 ... and more careful design of preclinical studies.[115][116][117][118] One approach is to rely more on studying biopsies and ... "Neonatal infectious diseases: Evaluation of neonatal sepsis". Pediatric Clinics of North America. 60 (2): 367-89. doi:10.1016/ ... therapeutic drug monitoring is important to ensure adequate drug therapeutic level while at the same time preventing the drug ...
"Evaluation of PIK3CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer" ... While substantial preclinical data show an association with robust activation of the pathway and resistance to common therapies ... "US Food and Drug Administration. September 14, 2017.. *^ Holinstat M, Mehta D, Kozasa T, Minshall RD, Malik AB (August 2003). " ... Due to the association between p110α and cancer,[13] it may be an appropriate drug target. Pharmaceutical companies are ...
For research on pregnant women and fetuses, condition topics include preclinical risk studies, minimizing risk, no money (or ... Both for-cause compliance and not-for cause surveillance evaluations are conducted. ... Food and Drug Administration (FDA) regulation that covers clinical research conducted by pharmaceutical companies as well as ... the Food and Drug Administration added their first regulations protecting human research subjects, which were revised in 1981.[ ...
Preclinical and clinical research indicates that drugs inhibiting the reuptake of all three of these neurotransmitters can ... Wee, S; Woolverton, WL (2004). "Evaluation of the reinforcing effects of atomoxetine in monkeys: Comparison to methylphenidate ... Abuse, National Institute on Drug. "Drug-Related Hospital Emergency Room Visits". Retrieved 2016-04-04. ... For these drugs to be reinforcing, they must block more than 50% of the DAT within a relatively short time period (. 3.0.CO;2-8 ...
... effect of non-steroidal anti-inflammatory drugs on Alzheimer's disease pathology". CNS & Neurological Disorders Drug Targets. ... a b Neuropsychological Features of Mild Cognitive Impairment and Preclinical Alzheimer's Disease. Acta Neurologica Scandinavica ... Economic Impact of Dementia in Developing Countries: An Evaluation of Costs of Alzheimer-type Dementia in Argentina. ... al., edited by Brian K. Alldredge ... et (2013). Applied therapeutics : the clinical use of drugs (10th udgave). Baltimore: ...
... these pre-clinical studies allow that 13(S)-HODE, made at least in part by eosinophils and operating through TRPV1, may be ... 13-HODE axis inhibits the development of drug-induced colon cancer as well as the growth of human colon cancer cell explants.[ ... "A re-evaluation of 9-HODE activity at TRPV1 channels in comparison with anandamide: Enantioselectivity and effects at other ...
"U.S. food and Drug Administration. U.S. Government. Retrieved 11 September 2017.. ... Echocardiography is an essential tool in cardiology, assisting in evaluation of heart valve function, such as stenosis or ... At the stage of scientific preclinical research, the technique of acoustic radiation force was implemented as a prototype in ... Diagnostic and therapeutic ultrasound equipment is regulated in the USA by the Food and Drug Administration, and worldwide by ...
"The anti-ageing potential of a new jasmonic acid derivative (LR2412): in vitro evaluation using reconstructed epidermis ... Pre-clinical development. *Protein-directed dynamic combinatorial chemistry. *Discovery and development of proton pump ... "The drug development process. Step 4: FDA drug review". US Food and Drug Administration. 4 January 2018. Retrieved 18 December ... New Drug Application[edit]. When a drug is developed with evidence throughout its history of research to show it is safe and ...
United States Food and Drug Administration. Guidance for Industry: Source Animal, Product, Preclinical, and Clinical Issues ... Center for Biologics Evaluation and Research. *^ "The Australian National Health and Medical Research Council's 2005 statement ... Kress, J. M. (1998). "Xenotransplantation: Ethics and economics". Food and Drug Law Journal. 53 (2): 353-384. PMID 10346691.. ... The Food and Drug Administration (FDA) has also stated that if a transplantation takes place the recipient must undergo ...
Organovo anticipates that the bioprinting of human tissues will accelerate the preclinical drug testing and discovery process, ... Research, Center for Biologics Evaluation and. "Questions about Tissues - Tissue and Tissue Product Questions and Answers". www ... Many other new drugs are under development for transplantation.[127] The emerging field of regenerative medicine promises to ... New Drugs in Transplantation, EBMT Meeting, France, March 2007 C. Paillet, Pharmacist, Pharm D. C. Renzullo, Pharmacist, Pharm ...
152.0 152.1 Lipton SA (2006). "Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond". Nat Rev Drug ... Allegri RF, Butman J, Arizaga RL, et al. (Agosti 2007). "Economic impact of dementia in developing countries: an evaluation of ... 21.0 21.1 Arnáiz E, Almkvist O (2003). "Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's ... Solomon B (Juni 2007). "Clinical immunologic approaches for the treatment of Alzheimer's disease". Expert Opin Investig Drugs ...
Drug potency and binding affinity[edit]. Binding affinity data alone does not determine the overall potency of a drug. Potency ... Nimczick M, Pemp D, Darras FH, Chen X, Heilmann J, Decker M (August 2014). "Synthesis and biological evaluation of bivalent ... there have been many ligands that have reported successful pre-clinical animal studies.[21][22][19][25][26][27] Given that some ... This plays an important role in pharmacology, where drugs that are non-selective tend to have more adverse effects, because ...
Immunosuppressive drugs[edit]. Immunosuppressive drugs help manage organ transplantation and autoimmune disease. Immune ... oligodeoxynucleotides and glucans are involved in clinical and preclinical studies. ... "Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative ... Immunomodulatory imide drugs (IMiDs). thalidomide and its analogues (lenalidomide, pomalidomide, and apremilast) ...
Drug Delivery: drugs can be incorporated into the microbubble's lipid shell. The microbubble's large size relative to other ... Ultrasound imaging allows real-time evaluation of blood flow.[20]. *Destruction of microbubbles by ultrasound[21] in the image ... There are two forms of contrast-enhanced ultrasound, untargeted (used in the clinic today) and targeted (under preclinical ... drug delivery vehicles like liposomes may allow a greater amount of drug to be delivered per vehicle. By targeted the drug- ...
Interpretation and Relevance in Drug Safety Evaluation.. [Peter Greaves] -- The new 4,SUP,th,/SUP, edition of Histopathology of ... Preclinical Toxicity Studies is now completely in full color and continues to describe the pathology found in drug safety ... drug_safety_evaluation> ;. schema:name "Histopathology of Preclinical Toxicity Studies : Interpretation and Relevance in Drug ... Histopathology of Preclinical Toxicity Studies : Interpretation and Relevance in Drug Safety Evaluation.. Author:. Peter ...
... which provided estimates of single drug effects together with a quantitative model-based evaluation framework for evaluation of ... Preclinical research is important for defining drugs and regimens which should be carried forward to human studies. This thesis ... Evaluations and Experimental Design Recommendations for Preclinical Studies of Anti-tuberculosis Drugs. Chen, Chunli Uppsala ... tuberculosis, pharmacokinetics-pharmacodynamics, drug-drug interactions, mixed effect models, pharmacometrics National Category ...
Preclinical Saxfety Evaluation of Biological Oncology Drugs (Theresa Reynolds, BA, DABT (Genentech)). ... Preclinical Safety Evaluation of Immunotoxins (Jennifer G. Brown, PhD, Joycelyn Entwistle, PhD, Nick Glover, PhD, and Glen C. ... Preclinical Safety Study Design Templates and Estimated Costs (Gary W. Wolfe, PhD, DABT (Summit Drug Development Services)). ... Preclinical Evaluation of Cancer Hazard and Risk of Biopharmaceuticals (Joy A. Cavagnaro, PhD, DABT, RAC (Access BIO)). ...
From the Afterword by Anthony D. Dayan Proper preclinical safety evaluation can improve the predictive value, lessen the time ... With chapters contributed by experts in their specific areas, Preclinical Safety Evaluation of Biopharmaceuticals: A Science- ... straightforward reference for professionals involved in preclinical drug development, including scientists, toxicologists, ... of safety assessments for small molecules with those for biopharmaceuticals Addresses all aspects of the preclinical evaluation ...
Evaluation of Drug Candidates for Preclinical Development: Pharmacokinetics, Metabolism, Pharmaceutics, and Toxicology - Author ... Keywords: Charles Davis, evaluation of drug candidates, assessment of drug candidates, evaluation of potential drug compounds, ... Evaluation of Drug Candidates for Preclinical Development: Pharmacokinetics, Metabolism, Pharmaceutics, and Toxicology. 101,10€ ... assessment of potential drug compounds, ADMET, drug transporters, cytochrome P-450 and drug-drug interactions, plasma protein ...
... ... which can be relevant due to the fact that the toxicity is a common problem of the available antiepileptic drugs. Furthermore, ... of epileptic patients are still inadequately controlled by standard drug therapy. For this reason, it continues to be important ... of the compounds presented lower toxicity than the antiepileptic drugs lamotrigine, carbamazepine and phenytoin. In addition, ...
... primary human hepatocytes may represent the most appropriate experimental system for the evaluation of CYP induction in humans ... inhibition and induction are the key mechanisms in drug-drug interactions. Aside from clinical studies, ... Preclinical evaluation of drug-drug interaction potential: present status of the application of primary human hepatocytes in ... Cytochrome P450 (CYP) inhibition and induction are the key mechanisms in drug-drug interactions. Aside from clinical studies, ...
In this study, we performed a comprehensive preclinical comparison of tiotropium with other long-acting muscarinic antagonists ... Preclinical evaluation of long-acting muscarinic antagonists: comparison of tiotropium and investigational drugs.. @article{ ... Preclinical evaluation of long-acting muscarinic antagonists: comparison of tiotropium and investigational drugs.}, author={ ... Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development. *Juergen Wess, R. M. Eglen, Dinesh ...
These results highlight the potential for CYP 2D6-mediated drug-drug interactions with primaquine and indicate that the SSRI/ ... Additionally, CYP 2D6-mediated drug-drug interactions can be considered when examining the possible causes of human primaquine ... Factors such as CYP 2D6 poor metabolizer status and/or co-administration of drugs that inhibit/interact with CYP 2D6 could ... The SSRI/SNRI classes of drug displayed a range of inhibitory activities on CYP 2D6-mediated metabolism of primaquine in vitro ...
... preclinical drug evaluation, -omics methods.. Abstract:Preclinical drug development is an essential step in the drug ... Preclinical drug development is an essential step in the drug development process where the evaluation of new chemical entities ... Keywords: Drug testing, proteomics, transcriptomics, mass spectrometry, preclinical drug evaluation, -omics methods. ... omics methods and platforms for mechanistic evaluation of drug candidates and speed-up of the preclinical evaluation steps. ...
"Drug Evaluation, Preclinical" by people in this website by year, and whether "Drug Evaluation, Preclinical" was a major or ... "Drug Evaluation, Preclinical" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ... Below are the most recent publications written about "Drug Evaluation, Preclinical" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Drug Evaluation, Preclinical". ...
To address this problem, we developed and experimentally validated a general computational framework for drug target discovery ... The identification of drug targets is highly challenging, particularly for diseases of the brain. ... Pre-clinical evaluation of Csf1R blockade in mice. To evaluate the effect of Csf1R blockade on gene network expression and ... Whilst pre-clinical testing in animal models remains the mainstay for determining efficacy of candidate antiepilepsy drugs19, ...
... ... Preclinical evaluation of M30 and M65 ELISAs as biomarkers of drug induced tumor cell death and antitumor activity. 2008, 7 (3 ... Specific demonstration of drug-induced tumour cell apoptosis in human xenografts models using a plasma biomarker. ... By contrast, M65 did not detect a drug-induced increase in circulating antigen levels at day 5. However, M65 plasma levels ...
Drugs. ENMD-2076 [2-(phenylvinyl-4-[4-methylpiperazin-1-yl])-6-(5-methy-2H-pyrazol-3-yl-amino)-pyrimidine)] was provided by ... Evaluation of cytotoxicity. To evaluate cytotoxic effects, the sulforhodamine B (SRB) method was used as previously described ( ... Preclinical activity of a novel multiple tyrosine kinase and aurora kinase inhibitor, ENMD-2076, against multiple myeloma. Br J ... Following treatment, the wells were washed with 1X PBS and incubated in drug free DMEM with 10% FBS for 7 days to allow for ...
Evaluation of preclinical antimalarial drugs, which can overcome direct-acting antivirals-resistant hepatitis C viruses, using ... Fingerprint Dive into the research topics of Evaluation of preclinical antimalarial drugs, which can overcome direct-acting ...
... numerous molecular markets in the pre-clinical evaluation as cancer drug targets. Save to give specific searches for routine ... Numerous molecular markets in the pre-clinical evaluation as cancer drug targets.. In addition, numerous molecular markets in ... the pre-clinical evaluation as cancer drug targets. Save to give specific searches for routine checking received nm. Contact ...
Results of search for su:{Drug evaluation, Preclinical} Refine your search. *Availability * Limit to currently available ... prepared by the staffs of Washington Drug Letter, the Food & Drug Letter, Drug GMP Report.. by United States. Food and Drug ... Drug bioscreening : fundamentals of drug evaluation techniques in pharmacology / by Emmanuel B. Thompson.. by Thompson, ... Drug bioscreening : drug evaluation techniques in pharmacology / Emmanuel B. Thompson.. by Thompson, Emmanuel B ...
Synthesis and pre-clinical evaluation of a new class of high-affinity 18F-labeled PSMA ligands for detection of prostate cancer ... Nat Rev Drug Discov. 2015;14:203-19.CrossRefPubMedGoogle Scholar ... Preclinical evaluation of a tailor-made DOTA-conjugated PSMA ... Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular ... In vivo evaluation. The six compounds were assessed in a mouse model of prostate cancer by μPET/CT imaging at 1 h, 2 h, 4 h and ...
Preclinical Evaluation of MEDI0641, a Pyrrolobenzodiazepine Conjugated Antibody-Drug Conjugate Targeting 5T4. Harper, Lloyd, ... Preclinical Evaluation of MEDI0641, a Pyrrolobenzodiazepine Conjugated Antibody-Drug Conjugate Targeting 5T4. Mol Cancer Ther; ...
The claims of eight cisplatin analogues as viable alternatives to the parent drug are discussed in terms of their toxicities, ... Drug Evaluation, Preclinical * Kidney / drug effects * Mice * Neoplasms, Experimental / drug therapy * Nucleoproteins / ... Preclinical studies identifying carboplatin as a viable cisplatin alternative Cancer Treat Rev. 1985 Sep;12 Suppl A:21-33. doi ... The claims of eight cisplatin analogues as viable alternatives to the parent drug are discussed in terms of their toxicities, ...
Preclinical Evaluation Plattform For Drug Candidates. website. Preclinical Evaluation Plattform For Drug Candidates. ... Using PET for the Evaluation of Innovative Analgetics with Dual Mode of Action (Dual²PET). Innovative drugs targeting two modes ... This novel approach in drug development is targeting at faster and more predictable means to evaluate and provide innovative ... These ‚dual modulators come with the decisive advantage of avoiding the application of different drugs with individual ...
PRECLINICAL EVALUATION. Extensive pharmacological evaluation has shown that drug concentrations that have an antiproliferative ... Supko JG, Hickman RL, Grever MR, Malspeis L. Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. Cancer ... Bertram J, Palfner K, Hiddemann W, Kneba M. Increase of P-glycoprotein-mediated drug resistance by hsp 90β Anticancer Drugs. ... A novel drug for the treatment of malignant diseases should have a mechanism of action different from those known for ...
... pharmacology and medicine for improved drug target discovery through the efforts of our research laboratories and core ... Drug Evaluation. *in-vitro testing. *in-vivo testing. *small molecules. *biologics. Drug Discovery. *CRC for Cancer ... Approaches include in vitro and in vivo screening, small molecule high-throughput screening, pre-clinical imaging and ... Evaluation of Youth Cancer Services Phase II, 2013 to 2017. *Phase 1 implementation and evaluation of a model of youth friendly ...
... ... This confirmed the enhancing properties of Pheroids™ in the delivery of drugs into the cells. The MTT assay was further adapted ... Enhancing ARV treatment may be accomplished by the use of the Pheroid™ drug delivery system. Pheroids™ consists mainly of fatty ... stability as well as the low efficacy of these drugs. Most of the above mentioned problems and obstacles related to ARVs and ...
This updated reference is essential for those involved in drug safety evaluation, including pathologists, toxicologists and ... specific tumor types induced by drugs in rodents, and new drug-induced pathologies and lesions ... of Preclinical Toxicity Studies is now completely in full color and continues to describe the pathology found in drug safety ... updated bibliography and discusses new drug-induced pathologies and applicable species comparisons to aid in the preclinical ...
Formulation and preclinical evaluation of Anti-inflammatory activity of Triticum aestivum * Sai Krishna Priya Dasari Department ... Formulation and preclinical evaluation of Anti-inflammatory activity of Triticum aestivum. JDDT [Internet]. 15May2021 [cited ... Immediate Drug Release Dosage Form: a Review. J Drug Deliv Ther. 2013; 3(2):155-61. ... Formulation and Evaluation of Immediate Release Tablet of Valsartan. Int J Pharm Sci Res [Internet]. 2015; 6(2):808. Available ...
Results of search for su:{Drug Evaluation} and su-to:Drug evaluation, Preclinical ... prepared by the staffs of Washington Drug Letter, the Food & Drug Letter, Drug GMP Report.. by United States. Food and Drug ... Drug bioscreening : fundamentals of drug evaluation techniques in pharmacology / by Emmanuel B. Thompson.. by Thompson, ... Drug bioscreening : drug evaluation techniques in pharmacology / Emmanuel B. Thompson.. by Thompson, Emmanuel B ...
Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing. The established urinary ...
Drug Evaluation, Preclinical. Female. Guanine / analogs & derivatives*, diagnostic use, pharmacokinetics, toxicity. Herpesvirus ... Preclinical safety evaluation of 18F-FHBG: a PET reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1- ... Previous Document: Radiosynthesis and preclinical evaluation of 11C-ABP688 as a probe for imaging the metabotropic glut.... ... The Food and Drug Administration has approved FHBG as an Investigational New Drug.. ...
  • Preclinical evaluation of M30 and M65 ELISAs as biomarkers of drug induced tumor cell death and antitumor activity. (
  • AT-406 is an orally-active, small molecule drug designed to promote programmed cell death (apoptosis) in tumor cells by blocking the activity of at least three "inhibitors of apoptosis proteins" or IAPs (including XIAP, c-IAP1, and c-IAP2) to create conditions in which apoptosis can proceed. (
  • AT-406 has also been shown to work synergistically with conventional chemotherapeutic and targeted agents (such as tyrosine kinase inhibitors) in preclinical tumor models. (
  • ARLINGTON, Va., May 7 /PRNewswire-FirstCall/ -- Champions Biotechnology, Inc. (OTC Bulletin Board: CSBR), a company engaged in the development of advanced preclinical platforms and tumor specific data to enhance the value of oncology drugs, today announced that it has established an agreement with ImClone Systems Incorporated for the preclinical evaluation of certain therapeutic antibodies in ImClone's clinical development pipeline. (
  • Champions Biotechnology, Inc. is engaged in the development of advanced preclinical platforms and predictive tumor specific data to enhance and accelerate the value of oncology drugs. (
  • The Company's Preclinical Platform is a novel approach based upon the implantation of primary human tumors in immune deficient mice followed by propagation of the resulting xenografts (Biomerk Tumorgrafts(TM)) in a manner that preserves the biological characteristics of the original human tumor. (
  • The Company also offers its predictive preclinical platform and tumor specific data to physicians for personalized patient care. (
  • Based on tumor proliferation, location, and penetrance, we selected one of these Nf1 GEM models for preclinical drug evaluation. (
  • Preclinical data evaluating VB-111 in a comprehensive set of in vivo studies employing the Lewis Lung metastasis mouse model showed the compound to be safe and specific, with a 90% reduction in tumor burden of lung metastases after only one injection. (
  • The preclinical findings coupled with the safety and tolerability VB-111 demonstrated in the Phase 1 patient study support the continued clinical evaluation of the compound in specific tumor types of advanced metastatic cancer, and underscores the potential for VB-111 as a broad-spectrum cancer therapy. (
  • Antibody-drug conjugates (ADCs) are a novel anti-tumor drug that combines antibodies with targeted properties and strong cytotoxic drugs. (
  • ADC has since then been gifted the powerful killing power of small molecule drugs and also the high targeting power of pure monoclonal antibodies, making it a research focus of tumor targeted therapy. (
  • This thesis aims to characterize the population pharmacokinetics and exposure-response relationships of anti-tubercular drugs alone and in combinations, and to suggest experimental designs for preclinical settings. (
  • The goal is to provide a comprehensive reference book for the preclinicaldiscovery and development scientist whose responsibilities span target identification, lead candidate selection, pharmacokinetics, pharmacology, and toxicology, and for regulatory scientists whose responsibilities include the evaluation of novel therapies. (
  • It includes sections on pharmacokinetics and drug metabolism, integration of pharmaceutical development, and predictive safety assessment. (
  • In particular, preclinical drug development phases include deep analysis of drug candidates' interactions with biomolecules/targets, their safety, toxicity, pharmacokinetics, metabolism by use of assays in vitro and in vivo animal assays. (
  • It is important to understand the mechanisms of action and the pharmacokinetics of antiepileptic drugs (AEDs) so that these agents can be used effectively in clinical practice, especially in multidrug regimens (see the image below). (
  • You will learn that the effects of a drug depend not only on its actions ( i.e., pharmacodynamics) , but also on how an individual handles the drug (i.e., pharmacokinetics). (
  • In vivo testing of novel lead compounds, biologics, or repurposed drug candidates in relevant animal models for pharmacokinetics, dose-range finding, target engagement, in vivo efficacy, and/or preliminary rodent tolerability studies. (
  • This RFP supports lead optimization, in vivo pharmacokinetics, preclinical target engagement, preclinical efficacy, and/or preliminary rodent tolerability studies. (
  • Preclinical studies were conducted to evaluate the metabolic stability, plasma protein binding, pharmacokinetics, toxicity, and efficacy of CD101 at various dose levels. (
  • Drug bioscreening : drug evaluation techniques in pharmacology / Emmanuel B. Thompson. (
  • Researchers at Peter Mac strive to link recent advances in genetics, genomics, cell and chemical biology, pharmacology and medicine for improved drug target discovery through the efforts of our research laboratories and core facilities. (
  • To identify potential toxicities, we consulted the existing evidence from AAV gene therapy for other nervous system disorders (animal toxicology and human studies) and from the clinical pharmacology of conventional analgesic drugs. (
  • This objective is pursued through the generation of new knowledge thanks to research in experimental pharmacology, the study of the pathogenetic mechanisms responsible for diseases, the development and / or refinement of experimental models, the evaluation of the efficacy and safety of new drugs (or repositioned drugs) in appropriate cell and animal models of pathology. (
  • In summary, in this thesis the population pharmacokinetic-pharmacodynamic models of first-line drugs in mice were characterized through linking each population pharmacokinetic model to the MTP model. (
  • Lastly, experimental designs were optimized and recommended to both pharmacokinetic and pharmacodynamic studies for preclinical settings. (
  • The course will outline how pharmacodynamic and pharmacokinetic studies are applied in the discovery and development of new drugs and the processes that follow to turn the new drug into a medicine that can be approved for use in patients. (
  • Her research lay in the field of biomaterials and advanced drug carrier systems including the design and the development of polymer and lipid based micro‐ and nanoscale carriers, their biological evaluation in in vitro cell cultures (toxicity, mechanism of action, intracellular drug release) and also their pharmacokinetic and dynamic impact in vivo (using relevant animal models of the diseases). (
  • In addition, the most active compounds did not show notable cytotoxicity in in vitro experiments conducted in several cell lines (relative cell proliferation higher than 50% at 30 μM), which can be relevant due to the fact that the toxicity is a common problem of the available antiepileptic drugs. (
  • Sakai, Y. A novel in vitro system, the integrated discrete multiple organ cell culture (IdMOC) system, for the evaluation of human drug toxicity: comparative cytotoxicity of tamoxifen towards normal human cells from five major organs and MCF-7 adenocarcinoma breast cancer cells. (
  • Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. (
  • Using two different apoptotic markers, the kinetics of cell death induced by AZD1152 was first characterized in vitro in three different cell lines and shown to peak 5 to 7 days after drug addition. (
  • Assess key technologies for predicting drug safety in the earliest stages of discovery and clinical development with this report's comprehensive analysis of emerging approaches across in silico, in vitro and in vivo preclinical technologies. (
  • One of the primary goals of preformulation studies is to identify the physicochemical characteristics of a drug candidate that predict drug product performance in-vitro and in-vivo . (
  • The in silico and in vitro mechanistic evaluation indicated the potential of 16b as a lead for the development of novel anticancer agents against gastric cancer cells. (
  • Historically, drug discovery research has relied on two-dimensional in vitro assays (that is, cell monolayers cultured on plastic substrata) and in vivo animal models. (
  • Although 3D cell culture promises to provide a more relevant in vitro model for drug screening, there is still work to be done to see how these results actually translate to the clinic. (
  • Dr. Vulto acknowledges that "reproducing the 3D microenvironment is essential for developing physiologically relevant in vitro model systems in drug discovery. (
  • Histopathology of Preclinical Toxicity Studies : Interpretation and Relevance in Drug Safety Evaluation. (
  • I thought you might be interested in this item at Title: Histopathology of Preclinical Toxicity Studies : Interpretation and Relevance in Drug Safety Evaluation. (
  • edition of Histopathology of Preclinical Toxicity Studies is now completely in full color and continues to describe the pathology found in drug safety studies in laboratory animals with an evidence-based discussion of the relevance of these findings to the clinical investigation of new drugs for humans. (
  • Preclinical research is important for defining drugs and regimens which should be carried forward to human studies. (
  • 7. Comparison of Preclinical Development Programs for Small Molecules (Drugs/Pharmaceuticals) and Large Molecules (Biologics/Biopharmaceuticals): Studies, Timing, Materials, and Costs ( Christopher Horvath, DVM, MS, DACVP (Archemix Corp.) ). (
  • Aside from clinical studies, primary human hepatocytes may represent the most appropriate experimental system for the evaluation of CYP induction in humans. (
  • Herein, we present a comprehensive summary of current state-of-the art approaches and techniques used in preclinical studies. (
  • Fluorescence-based viability assay for studies of reactive drug intermediates. (
  • Definitive studies have demonstrated that adhesion of leukemia and lymphoma cells to extracellular matrices or stromal cells protects them against the toxicity of cytoreductive chemotherapy drugs. (
  • Thereby, we identified required preclinical studies and charted a hypothetical path towards a future phase I/II clinical trial in the oncology-palliative care setting. (
  • Therefore, the subsequent review on clinical translation and preclinical toxicology studies is predicated on a future plan to translate AAV gene therapy first in the palliative oncology setting. (
  • Preclinical toxicity studies of up to 6 months in rats and 9 months in monkeys indicated an excellent safety profile, supporting the clinical testing of the compound. (
  • Both preclinical studies showed only "moderate" positive effects. (
  • The ALS Therapy Development Institute, which studies the motor-neuron disease amyotrophic lateral sclerosis, has concluded - through its own animal studies - that several compounds that failed clinical trials entered human testing on the basis of poorly conducted or poorly designed preclinical experiments 1 . (
  • The United States Food and Drug Administration formulated the "Animal Rule" to facilitate use of validated animal models for conducting anti-viral efficacy studies. (
  • Institutional Ethics Committee clearance for clinical trials requires as a prerequisite, data from preclinical animal studies and acute, subacute toxicity tests. (
  • These objectives are pursued through preclinical and clinical research, technical-scientific and regulatory evaluation of the preclinical and clinical studies on new drugs, research and evaluation on the benefit-risk profile and on the place in therapy of drugs in the post- authorization phase. (
  • If a drug candidate is predicted to be BCS I (soluble and permeable), a simple formulation strategy can be employed for the GLP tox and first-in-human studies. (
  • April 21 /PRNewswire/ -- Ascenta Therapeutics announced today that the results of preclinical studies of its orally-active, small molecule, pro-apoptotic agent, AT-406, have been presented at the 100th Annual Meeting of the American Association for Cancer Research (AACR), in Denver, Colorado (Abstract # 1917). (
  • Studies suggest that our Biomerk Tumorgrafts provide an accelerated and more predictive platform for the evaluation of oncology drugs. (
  • These preclinical studies demonstrated that CD101 is chemically and metabolically stable, well tolerated with no hepatotoxicity, and efficacious as an antifungal agent. (
  • TEL AVIV, Israel--(BUSINESS WIRE)--Apr 19, 2010 - VBL Therapeutics today announced positive results from preclinical and Phase 1 studies evaluating the company's lead anti-cancer agent, VB-111 - a first-in-class, targeted biological agent shown to work via dual-action, anti-angiogenic and vascular disruptive mechanism of action - in metastatic cancer. (
  • Preclinical data evaluating VB-111 in a comprehensive set of in vivo studies employing the Lewis Lung metastasis mouse model showed the compound to be safe and specific with activity only in the metastatic lesion themselves. (
  • More than ever, it is extremely important that preclinical studies are conducted in a similar way compared to the application of the device in the clinical setting. (
  • Due to its cancer preventive activity sarcophytol A was advanced to National Cancer Institute sponsored preclinical evaluation studies [ 4 ]. (
  • Dr. Petrukhin is optimizing the compound for evaluation in additional preclinical studies. (
  • In particular, we will review the potential of new, -omics methods and platforms for mechanistic evaluation of drug candidates and speed-up of the preclinical evaluation steps. (
  • We contend that a lack of emphasis on evidence for the efficacy of drug candidates is all too common in decisions about whether an experimental medicine can be tested in humans. (
  • Consequently, such drugs are attractive candidates for "repurposing" as anti-viral agents. (
  • If a drug molecule is predicted to have challenging oral bioavailability [BCS II (insoluble, but permeable), or IV (insoluble, poor permeability)], choosing an appropriate formulation strategy for tox and human Phase 1 is critical to ensure the solubility and bioavailability of those drug candidates is maximized in order to realize its full potential for safety and efficacy evaluation in animal and human. (
  • As part of a continuing search for new potential anticancer candidates, we describe the synthesis, cytotoxicity and mechanistic evaluation of a series of 4-oxoquinoline-3-carboxamide derivatives as novel anticancer agents. (
  • Champions Biotechnology leverages its preclinical platform to evaluate drug candidates and to develop a portfolio of novel therapeutic candidates through pre-clinical trials. (
  • Instead, separate and distinct discovery research, preclinical development, and clinical development divisions were created within many companies during the 1980s and 1990s, Because of their isolation, scientists in the discovery research divisions often were advancing drug candidates into preclinical development that had marginal drug-like properties. (
  • Lacking optimal drug-like properties often caused these drug candidates to fail in preclinical or clinical development. (
  • In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). (
  • She is founder and past chair of the BIO Preclinical Safety Expert Group (BioSafe) and was the U.S. BIO Representative to the 2006 ABPI/BIA Early Stage Clinical Trials Taskforce.Dr. Cavagnaro is currently North American Chair of the Drug Information Association-Biotech SIAC and Chair of the Clinical and Regulatory Affairs Committee of the American Society of Gene Therapy. (
  • Although significant advances are occurring in epilepsy research, about 30% of epileptic patients are still inadequately controlled by standard drug therapy. (
  • Preclinical Evaluation of Tysabri as a Novel Adjuvant Therapy against Drug Resistant B-ALL. (
  • The Alzheimer's Drug Discovery Foundation (ADDF) and The Association for Frontotemporal Degeneration (AFTD) seek to accelerate and support innovative small molecule and biologic (antibodies, oligonucleotides, peptides, gene therapy) drug discovery programs for FTD through this request for proposals (RFP). (
  • BPaL was approved by the US Food and Drug Administration (FDA) on August 14, 2019, based in part on results from the Nix-TB trial in South Africa, which included patients with XDR TB or multidrug-resistant (MDR) TB who failed or were intolerant of prior therapy ( 1 ). (
  • LRRC15 has limited expression in normal tissue and thus may be an attractive target for drug therapy. (
  • In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. (
  • The team has made significant progress in designing and evaluating a cone-targeted optogenetic therapy for evaluation in a future clinical trial. (
  • She serves on a number of scientific advisory boards and lectures internationally in the area of preclinical development of novel therapies. (
  • 2. Methods of Production of Biopharmaceutical Products and Assessment of Environmental Impact ( Patricia D. Williams, PhD (Summit Drug Development Services) ). (
  • Readers will understand why absorption-distribution-metabolism-excretion-toxicology (ADMET) is key in drug development. (
  • Preclinical drug development is an essential step in the drug development process where the evaluation of new chemical entities occurs. (
  • It aims at using positron emission tomography (PET), a non-invasive, repeatedly applicable and quantitative method, as a genuine technique in the development and optimization of novel drugs with dual modes of action. (
  • This novel approach in drug development is targeting at faster and more predictable means to evaluate and provide innovative drugs. (
  • The Vaccine Development Services program offers a collection of preclinical services to support the development of vaccines intended for use in the investigation, control, prevention, and treatment of a wide range of infectious agents (other than HIV). (
  • In the NCI, Chemoprevention Branch drug development program, potential chemopreventive agents are evaluated for efficacy against chemical carcinogen-induced tumors in animal models. (
  • Encompassing an industry-led agenda including academic keynote presentations, SMi's 9th annual conference on Imaging in Cancer Drug Development will be a unique opportunity to witness presentations on the current developments surrounding: oncology and diagnostic imaging modalities, drug development and clinical development alongside networking with key industry professionals. (
  • This will encourage attendees to discuss growth in the field and exchange ideas, therefore driving the field forward and ensuring sufficient treatment of the key issues surrounding oncology imaging and drug development. (
  • More-thorough assessments of clinical potential before trials begin could lower failure rates and drug-development costs. (
  • Clinical Drug Development explains the science behind the discovery and development of new drugs, from initial ideas through to clinical use in man. (
  • Students spend approximately 9 weeks on a project that follows the steps involved in a drug development project, with information drip fed to them at regular intervals for analysis and assessment. (
  • Our mission is to promote the discovery, development and testing of drugs in order to protect and improve public health. (
  • The development and biological evaluation of nanotechnology platforms for the delivery of therapeutic agents (including substances of natural origin) represent a further approach to the development of effective and safe drugs. (
  • Declining industrial productivity has forced companies to urgently address the areas of drug development that are most likely to lead to the failure of a new compound. (
  • Pharmacometric modeling and simulation and novel study methods such as adaptive designs are increasingly being applied in drug development to make the most of the data collected and to guide the choice of dose for clinical application. (
  • Understand the latest strategies to improve safety evaluation in early clinical development with this report's analysis of the latest approaches in exploratory and Phase I clinical trials. (
  • Rodent and non-rodent models used in drug development are expensive and the results do not always translate well to the human situations. (
  • When a compound enters preclinical development for a GLP tox study from the drug discovery stage, we face a question of how to develop a tox and clinical formulation that ensures the success of IND and first dose in human. (
  • According to Lipper, et al, poor biopharmaceutical properties of compounds is attributed to 39% of the failure of the new drug program under development. (
  • The biopharmaceutical properties generated during the drug candidate selection process, which is critical for the next step of formulation development and for selection of formulation technologies, include compound dissolution in simulated gastric and intestine fluids, solubility, and stability in simulated GI fluids, enzymatic stability, intestine membrane permeability, and modeling and simulation of animal and human PK and bioavailability. (
  • A Comprehensive Guide to Toxicology in Nonclinical Drug Development, Second Edition , is a valuable reference designed to provide a complete understanding of all aspects of nonclinical toxicology in the development of small molecules and biologics. (
  • This updated edition has been reorganized and expanded to include important topics such as stem cells in nonclinical toxicology, inhalation and dermal toxicology, pitfalls in drug development, biomarkers in toxicology, and more. (
  • AT-406 is in late-stage preclinical development and has demonstrated strong single-agent antitumor activity in multiple xenograft models of human cancer, including breast cancer, pancreatic cancer, prostate cancer, and lung cancer. (
  • Nonclinical Safety Assessment: A Guide to International Pharmaceutical Regulations provides a practical description of nonclinical drug development regulations and requirements in the major market regions. (
  • According to a report issued by the Tufts Center for the Study of Drug Development, these costs exceed $2.5 billion per successful compound. (
  • The Tufts report also noted that drug development is lengthy, often taking longer than a decade. (
  • Consequently, researchers and pharmaceutical executives alike are anxious to increase the efficiency of drug development. (
  • The implementation of model-based approaches in drug development helps to bring new, safe and effective medicines to patients more efficiently. (
  • Discover the early phase clinical trial drug development fundamentals through our Maxims. (
  • However, the value of previously obtained clinical information will be weakened for various reasons in the development of novel drugs of TCM. (
  • As drugs progress through this early stage of development, the Company plans to sell, partner or license them to pharmaceutical and/or biotechnology companies, as appropriate. (
  • Champions Biotechnology is dedicated to enhancing preclinical development tools, accelerating development and valuation of oncology drugs, and advancing personalized treatment with a goal to improve the lives of cancer patients globally. (
  • Drug discovery and development is a very complex, costly, and ti- consuming process. (
  • Companies have responded to these pressures by introducing new technologies and new strategies to expedite drug discovery and development. (
  • Drug discovery and development have traditionally been divided into three separate processes (i. e. , discovery research, preclinical development, and clinical development) that ideally should be integrated both organizationally and functionally. (
  • Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process. (
  • A linker-drug platform was built on the basis of a cleavable linker-duocarmycin payload for the development of new-generation antibody-drug conjugates (ADC). (
  • These concerns are important because conducting disease research and drug development in a manner that is not supported by science will have suboptimal implications for the humans who rely on that research, which encompass the entire population. (
  • Their goals include further testing in large animal models and development of a slow-release, drug-delivery system. (
  • The rapid development of ADC drugs has also brought new problems to preclinical safety evaluation. (
  • Proper preclinical safety evaluation can improve the predictive value, lessen the time and cost of launching new biopharmaceuticals, and speed potentially lifesaving drugs to market. (
  • The purpose of this study was to evaluate the antitumor activity of the Aurora and angiogenic kinase inhibitor ENMD-2076 against preclinical models of breast cancer with identification of candidate predictive biomarkers. (
  • Early Stage Drug Safety Strategies and Risk Management' is a report published by Business Insights that identifies the new predictive technologies which can facilitate the earlier termination of potentially unsuccessful compounds. (
  • Identify which companies are leading the field in safety prediction for new drugs, understand the strategic implementations for large pharma companies and examine the role of public-private consortia in solving key issues within this field of predictive safety. (
  • He points to a "revolutionary era" for predictive models in drug discovery. (
  • The Company believes that these Tumorgrafts closely reflect human cancer biology and their response to drugs is more predictive of clinical outcomes in cancer patients. (
  • That is, animal models do not and cannot have acceptably high predictive value for human response to drugs and disease. (
  • Pharmacodynamic interactions in combination therapies were quantitatively described by linking the MTP model to the General Pharmacodynamic Interaction (GPDI) model, which provided estimates of single drug effects together with a quantitative model-based evaluation framework for evaluation of pharmacodynamic interactions among drugs in combinations. (
  • The optimized design for assessing pharmacodynamic interactions in the combination therapies, which was based on EC20, EC50 and EC80 of the single drug, provided lower bias and imprecision than a conventional reduced four-by-four microdilution checkerboard design at the same total number of samples required, which followed the 3Rs of animal welfare. (
  • Cytochrome P450 (CYP) inhibition and induction are the key mechanisms in drug-drug interactions. (
  • Antiepileptic drugs should be used carefully, with consideration of medication interactions and potential side effects. (
  • These ‚dual modulators' come with the decisive advantage of avoiding the application of different drugs with individual pharmacodynamics and dosing. (
  • In conclusion, JNJ-39758979 is a potent and selective H 4 R antagonist that exhibited good preclinical and phase 1 safety in healthy volunteers with evidence of a pharmacodynamics effect in humans. (
  • Our approach, which utilizes preclinical pharmacodynamics and the genetically determined multimodal distributions of serum clearances, is a preclinical tool that may be able to predict the EBAs of various doses of new antituberculosis drugs. (
  • Preclinical data with H 4 R receptor antagonists have generated interest in exploring the use of such antagonists in humans. (
  • Ethical review boards must focus on clinical promise as well as safety to hold the first tests of drugs in humans to a higher standard, say Jonathan Kimmelman and Carole Federico. (
  • Moreover, Bial's drug had been tested at a range of doses in micethat made it impossible to estimate the most likely effective dose in humans. (
  • Favoured picks for the next commissioner of the US Food and Drug Administration (FDA) are likely to lower the current requirements that a drug must demonstrate efficacy in humans before entering the market. (
  • Innovations are required that can support the earlier termination of drugs which will be toxic in humans and cause rare events that are unlikely to be identified in clinical trials. (
  • What's more, the exposure of drug in humans cannot solve each problem. (
  • Moreover, the minimal motor and/or neurological impairment evaluated through the rotarod assay showed that around 52% of the compounds presented lower toxicity than the antiepileptic drugs lamotrigine, carbamazepine and phenytoin. (
  • Organized according to organ systems, this revision features a thoroughly updated bibliography and discusses new drug-induced pathologies and applicable species comparisons to aid in the preclinical safety assessment of new medicines. (
  • Pilling, A.M. The role of the toxicologic pathologist in the preclinical safety evaluation of biotechnology-derived pharmaceuticals. (
  • Safety requirements for the first use of new drugs and diagnostic agents in man : a review of safety issues in early clinical trials of drugs. (
  • This updated reference is essential for those involved in drug safety evaluation, including pathologists, toxicologists and pharmacologists working in corporate, government, academic and research settings. (
  • Preclinical safety evaluation of 18F-FHBG: a PET reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk's expression. (
  • In the wake of the tragedies, the French medicines safety agency (ANSM) ordered an examination of the information that the drug developer, Bial, based in Trofa, Portugal, had supplied to ethics committees and potential researchers before the trial (see ). (
  • The approaches for sample preparation of preclinical evaluation of safety and efficacy are addressed taking into consideration the shortcoming with the contemporary approaches. (
  • Early Stage Drug Safety Strategies and Risk Management: Maximizing opportunities towards achieving clinic. (
  • a href href industrial productivity has forced companies to urgently add. (
  • Major pharma companies have subsequently begun to implement an array of new technologies for drug safety prediction into the discovery phases of research. (
  • It is well known that many valuable safety information of TCM comes directly from clinical use, which can be perceived as more important reference for TCM safety evaluation, to some extent, even than that from animals. (
  • Compared with the previous clinical application, the changes of medicinal material source, the prescription composition, extraction technology, selected population, administration mode, dosage, excipients, can lead to functional changes of drug ingredients, which may affect the safety of novel drugs. (
  • Above all, in order to explore the safety risk of TCM, there is great necessity of toxicology research in drug safety evaluation of TCM. (
  • To evaluate drug safety, there are several deficiencies in current standard animal models, and we should pay more attention to morbid animal models. (
  • The ultimate goal of drug safety evaluation is to reduce the safety risk of clinical medication, rather than experimental animals. (
  • So there are some deficiencies to predict the safety of drugs in patients with the data generated from normal animals. (
  • Patients had frequent clinical and laboratory safety evaluations. (
  • His primary responsibilities at Gradient include assisting clients with evaluation of immunological data, and conducting risk-based human health and chemical safety evaluations. (
  • The methodologies presented here provide a framework for pre-emptive preclinical characterisation of nanoparticle safety. (
  • In conclusion, the data obtained indicate great potential for this new HER2-targeting ADC to become an effective drug for patients with HER2-positive cancers with a favorable safety profile. (
  • However, over the last several years, the attention has shifted more toward safety and the effect of the drug concentration on the surface of the balloon. (
  • So, whereas the first generation of preclinical testing has focused on efficacy, in the second generation, there will be more focus on fine-tuning the drug dosage, safety considerations, and the use of this technology in other applications. (
  • With rare exception, drug interventions cannot reach commercialization without safety and efficacy having first been demonstrated in animal models. (
  • It is also important to choose the right center for drug safety assessment. (
  • Because ADC can reduce the systemic toxicity of drugs, reduce the amount of cytotoxic drugs, increase the targeted distribution of drugs, and increase the safety of cytotoxic drugs, more and more are used to treat tumors. (
  • A consensus of an international panel on the present status and future research directions in the application of primary human hepatocytes in the evaluation of CYP-induction is presented here. (
  • Risk-benefit analysis in drug research : proceedings of an international symposium, held at the University of Kent at Canterbury, England, 27 March 1980 / edited by J.F. Cavalla. (
  • Research showed promising results and advantages in delivering drugs through oral and transdermal routes using Pheroid™ technology. (
  • SAN DIEGO , Sept. 15, 2017 /PRNewswire/ -- Afraxis Inc. announced today that it has won a Small Business Innovation Research (SBIR) Phase I award from the National Institute on Aging to advance its big data phenotypic profiling platform for CNS drug discovery. (
  • At a workshop of the US National Academy of Sciences in September, Robert Temple, a veteran at the FDA's Center for Drug Evaluation and Research, said that the agency largely left it to drug sponsors to evaluate their rationale that an experimental drug was likely to work. (
  • The Center is involved in many institutional tasks (participation in national and international committees, technical tables and working groups) and in different training, information and communication activities (teaching in University and Master courses, annual organization of conferences and workshops on the themes of drug evaluation and research, dissemination of data and information on web pages). (
  • Research investigating the pathogenic mechanisms underlying frontotemporal degeneration (FTD) is advancing, creating new targets for drug discovery. (
  • However, there remains a global gap in FTD drug discovery research. (
  • The company is headquartered in Malvern, Pennsylvania, and has a preclinical research facility in Shanghai, China. (
  • However, further toxicology research of TCM new drugs is still necessary. (
  • This Funding Opportunity Announcement (FOA) issued by the National Institute on Drug Abuse (NIDA), National Institutes of Health, solicits research applications from institutions/organizations that propose design, synthesis, and preclinical testing of potential treatment agents for drug addiction and/or relapse prevention. (
  • The purpose of this RFA is to stimulate research for the design, synthesis and pharmacological evaluation of new classes of compounds as potential treatment agents for cocaine, methamphetamine or cannabinoid addiction based on novel pharmacological interventions and molecular targets other than biogenic amine transporters. (
  • The ultimate goal of this initiative is to expand existing research scope and elicit research proposals that will identify new pharmacotherapy based on current and advanced molecular and neurobiological understanding of the pathology of drug addiction and its relapse in the brain. (
  • Arlene's research interests are in the area of drug delivery wildlife applications and nanomedicines. (
  • Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. (
  • Realize the full power of the drug-disease research network! (
  • Dr. Juan F. Granada discusses the current climate of preclinical research, lessons learned in evaluating drug-eluting technologies, common misconceptions, and what the future holds. (
  • What is the current state of preclinical research in drug-eluting peripheral vascular technologies? (
  • The issue is crucial, as public opinion is behind animal research, only if it helps develop better drugs. (
  • For example, the American Physiological Society ( apa ) (2017) states on its website: "Animals are used in research to develop drugs and medical procedures to treat diseases. (
  • For projects that require preclinical assessment of drugs and other reagents, the Chordoma Foundation has developed resources that are available to the research community, including 14 chordoma cell lines and 6 xenograft models . (
  • ABBV-085, an antibody-drug conjugate against LRRC15, conjugated to monomethyl auristatin E (MMAE), was studied in osteosarcoma patient-derived xenografts (PDXs) by the Pediatric Preclinical Testing Consortium (PPTC). (
  • Antibody-drug conjugates (ADCs) are a therapeutic strategy in which a cytotoxic payload is attached to an antibody against a surface protein expressed on cancer and/or cancer-associated stromal cells via a linker, with the goal of delivering the payload to these cells via antigen-antibody interaction and internalization. (
  • Regardless the fact that there is no specific guiding principle for ADC, and there must be a reasonable scientific explanation behind the experimental design in the preclinical trials of antibody drug conjugate drugs. (
  • Synopsis: Evaluation of pharmacological strategies designed to modulate the Warburg effect, enhance the activity of tyrosine kinase inhibitors and novel analogues of Temozolomide. (
  • Several tyrosine kinase inhibitors (TKIs) developed as anti-cancer drugs, also have anti-viral activity due to their ability to disrupt productive replication and dissemination in infected cells. (
  • Explaining the assessment of potential drug compounds, this is an ideal introductory reference for those new to drug discovery. (
  • Post, J.M. Human primary renal cells as a model for toxicity assessment of chemo-therapeutic drugs. (
  • Postmarketing Surveillance of New Drugs and Assessment of Risk. (
  • In addition, for projects requiring in vivo drug testing, the Chordoma Foundation will consider having them included for assessment as part of their Drug Screening Program . (
  • On 17 January 2016, a healthy man was declared brain-dead after receiving an experimental drug in a first-in-human trial in France. (
  • Students will need to determine appropriate experimental techniques to generate data for the drug discovery game. (
  • We must take all clinical factors into consideration when designing and evaluating preclinical models, such as whether predilatation or postdilatation are required or stents are placed, and it is vital that we properly evaluate results based on the design of the experimental study versus the clinical reality. (
  • This is an enlightening reference for scientists, medicinal chemists, and others working in drug discovery. (
  • To address this problem, we developed and experimentally validated a general computational framework for drug target discovery that combines gene regulatory information with causal reasoning ("Causal Reasoning Analytical Framework for Target discovery"-CRAFT). (
  • Despite advances in our understanding of disease processes at the molecular and cellular levels, modern drug discovery has failed to deliver improved rates of approval for mechanistically novel drugs 1 . (
  • Optimism that advances in gene discovery would facilitate the validation of mechanistically novel drug targets has yet to materialize, and there is a requirement for new approaches to target discovery and validation. (
  • This systems approach to disease modification is loosely termed the "signature reversion paradigm" and is orthogonal to traditional concepts of drug discovery. (
  • The Phase I six-month pilot aims to expand the capabilities of Afraxis' Enhanced Spine Profiling (ESP) - a patented platform that quantifies brain-wide synaptic structures (dendritic spines) and plasticity for drug discovery. (
  • In conjunction with this award, Afraxis is advancing solutions to overcome a critical bottleneck in late-phase preclinical discovery: large-scale CNS in vivo efficacy and toxicity evaluations. (
  • The histamine H 4 receptor (H 4 R) has attracted interest as a potential drug target since its discovery in 2000. (
  • Throughout the course, students are drip-fed data that they are required to analyse as a part of a drug discovery programme. (
  • The result determines the next step to be taken in the drug discovery process. (
  • Students are required to analyse data at regular intervals during the course, from which they determine the next step to be taken in the drug discovery process. (
  • Future improvements in drug discovery will include the modeling of a wider range of toxicities, such as hepatotoxicity, and formations of reactive metabolites that might lead to idiosyncratic toxicity. (
  • High-content screening is increasingly important for identifying toxicity endpoints in a drug discovery setting. (
  • In the course of this process, this permits Champions Biotechnology to evaluate oncology drugs for companies by using models that integrate prognostic testing with biomarker discovery. (
  • Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. (
  • There are various strategies for discovery and validation of repurposed drugs. (
  • The venture of drug discovery has started with random screening of crude plants such as reserpine, lavender, and opium, and latterly created the drug industry, which is the one of the most advanced industries in our society ( Giridhar, 2012 ). (
  • As a part of this industry, the drug discovery process had enormous investments into infrastructures. (
  • Specific demonstration of drug-induced tumour cell apoptosis in human xenografts models using a plasma biomarker. (
  • We show that the novel Aurora and Angiogenic kinase inhibitor ENMD-2076 has activity against preclinical models of breast cancer with more robust activity against TNBC. (
  • Although these systems still predominate, drug developers are beginning to doubt whether the familiar assays and animal models are adequate with respect to physiological relevance and clinical predictability. (
  • Drug-induced nephrotoxicity is an abiding concern, but it still lacks reliable models. (
  • Mouse models of human cancers afford unique opportunities to evaluate novel therapies in preclinical trials. (
  • Unlike the case of high-grade gliomas, for which multiple genetic, xenograft, and cell culture models have supported extensive biological and preclinical investigations, low-grade gliomas have been considerably more challenging to model and study. (
  • The intention of regulations, which require the use of animal models in such contexts, is to ensure that only safe and effective drugs end up being used by patients. (
  • Drugs inhibiting these targets may be available for preclinical evaluation in relevant chordoma models. (
  • The industry will see an impact from financing, M&As, advanced therapies, generic drugs, and the retail market in 2018. (
  • Collectively, these findings suggest that this Nf1 optic glioma model may be a potential preclinical benchmark for identifying novel therapies that have a high likelihood of success in human clinical trials. (
  • A novel drug for the treatment of malignant diseases should have a mechanism of action different from those known for established oncological therapeutics. (
  • However, clinical evaluation of therapeutics against infectious agents associated with high mortality, but low or infrequent incidence, is often unfeasible. (
  • The potential use of such agents as anti-viral therapeutics represents an attractive strategy for repositioning drugs approved by US Food and Drug Administration (FDA) as readily available medical countermeasures (MCMs) against such biological threats. (
  • Ascenta Therapeutics Announces Results of Preclinical Evaluation of AT-406 in Multiple Can. (
  • In the search for new therapeutics for the treatment of human African trypanosomiasis , many potential drug targets in Trypanosoma brucei have been validated by genetic means, but very few have been chemically validated. (
  • The vision is to produce methods for objective evaluation of chronic pain and methods for evaluation of therapeutics. (
  • Ataxia Daytime somnolence Hypokinesia Cognitive and performance impairments In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class. (
  • For the first time, a molecular chaperone was identified as the target molecule of an anticancer drug. (
  • Sm-p80-based schistosomiasis vaccine: double-blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission-blocking efficacy. (
  • To determine the potential of Tysabri as a single agent to decrease leukemia progression, we engrafted 5-7 weeks old NOD/SCID mice with primary drug resistant B-ALL labeled with lentiviral luciferase to allow monitoring of leukemia using noninvasive bioluminescent imaging. (
  • Evaluation of protective efficacy of CC-2 formulation against topical lethal dose of T-2 toxin in mice. (
  • So in order to predict the clinical toxicity of drugs more accurately, can we evaluate with morbid animal model? (
  • 3) Need to evaluate the distribution of ADC drugs, distribution, metabolism, excretion and material balance of small molecule drugs. (
  • For the purpose of this presentation, "drug-like" properties refer to the molecule's physicochemical, absorption-distribution-metabolism-excretion (ADME), and toxicological properties. (
  • The identification of drug targets is highly challenging, particularly for diseases of the brain. (
  • Whilst successful examples for the use of such "perturbation databases" have emerged 11 , 12 , new targets are not identified by this route and the method's reliance on chance overlap in expression profiles means a very large number of drugs may need to be profiled to find one with a suitable profile 13 . (
  • A second approach has therefore emerged that aims to map the underlying drivers and regulators of disease-related gene expression signatures as candidate drug targets 7 . (
  • Numerous molecular markets in the pre-clinical evaluation as cancer drug targets. (
  • The biotech company Alkeus is conducting a multi-center Phase II clinical trial for a drug (ALK-001) that targets the toxic build-up in the retina that is thought to cause degeneration and vision loss. (
  • Preclinical data suggest a role for the H 4 R in a variety of inflammatory diseases. (
  • In one, Bial had data for a different marketed drug showing it was more effective than Bial's drug at relieving pain in animals, but did not include that information in a summary figure. (
  • Secondarily, we evaluated the utility of allometry-based inter-species scaling derived from previously published data to predict the PK parameters, systemic clearance (CL) and the steady state volume of distribution (Vss) of these two drugs in prairie dogs, an animal model not tested thus far. (
  • We felt that the necessary preclinical data should be obtained from plants grown locally in view of contradictory reports about the use of a tea prepared from E. jambolana (3) and its lack of an antidiabetic effect on rats with streptozotocin (STZ)-induced diabetes (4). (
  • On the basis of these encouraging data, we plan to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration to allow us to begin human clinical trials with AT-406 later this year. (
  • Taken together, these data provide initial chemical validation of TryS as a drug target in T. brucei. (
  • Finally, Temozolomide (TMZ) is an important drug in the treatment of glioblastomas but its activity is reduced by resistance mechanisms including O6 methyl guanine methyltransferase (MGMT) and mismatch repair (MMR). (
  • In conclusion, this thesis has demonstrated that interfering with the metabolic phenotype of cancer can enhance the activity of existing drugs and identified novel analogues of TMZ that circumvent drug resistance mechanisms that hamper the efficacy of TMZ. (
  • Rapid molecular detection of drug resistance and growth-based drug susceptibility testing performed by the Centers for Disease Control and Prevention (CDC) and Florida Bureau of Public Health Laboratories yielded concordant results. (
  • We detected resistance to isoniazid, rifampin, the fluoroquinolones (levofloxacin and moxifloxacin), and an injectable (kanamycin), confirming a diagnosis of extensively drug-resistant TB (XDR TB). (
  • Not only this but CRC also has poor overall survival rates particularly in the advanced disease setting mainly due to drug resistance to standard-of-care chemotherapeutics. (
  • One of the mechanisms of drug resistance is the upregulation of the anti-apoptotic protein FLIP (Fas-associated death domain (FADD)-like interleukin-1 b-converting enzyme (FLICE) Inhibitory Protein) which has been shown to be overexpressed in various types of cancer. (
  • Although many strains of MRSA remain sensitive to fusidic acid, there is a low genetic barrier to drug resistance (a single point mutation is all that is required), fusidic acid should never be used on its own to treat serious MRSA infection and should be combined with another antimicrobial such as rifampicin when administering oral or topical dosing regimens approved in Europe, Canada, and elsewhere. (
  • However, resistance selection is low when pathogens are challenged at high drug exposure. (
  • Drug Evaluation, Preclinical" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • The Company's preclinical pipeline includes the oral multi-IAP antagonist AT-406, and an HDM2-p53 inhibitor program. (
  • Preclinical evaluation of long-acting muscarinic antagonists: comparison of tiotropium and investigational drugs. (
  • The Food and Drug Administration has approved FHBG as an Investigational New Drug. (
  • Developed, contracted, and monitored preclinical testing program for an investigational new drug. (
  • See what these investigational drugs may have to offer in the fight against COVID-19. (
  • There are more Investigational New Drug (IND) filings that need to be submitted in China than in the West, and changes in domestic regulatory environment should also be closely watched. (
  • Inflammation and ulceration induced by systemic drug administration. (
  • In this thesis, various pharmacological strategies designed to enhance the activity of existing therapeutic drugs were evaluated. (
  • We conclude that primary human hepatocytes represent an appropriate model for mechanistic evaluation of CYP induction and as a screening tool for CYP induction potential of xenobiotics. (
  • Several marine natural products are currently in pre-clinical and clinical evaluation, others show promising biological activities [ 1 ]. (
  • ADC drugs have the characteristics of both small molecule cytotoxic drugs and macromolecular antibody drugs. (
  • Therefore, toxicology tests need to pay attention to the toxicity of both small molecule drugs and macromolecular antibodies. (
  • The toxicity is mostly from the small molecule drug payload, although the antibody part can also be toxic (ADCC and CDC). (
  • It can be combined with toxicology test, and hERG test is needed for new small molecule drugs. (
  • The structure and process of ADC drugs are complex, and the molecular type, the attachment site, the polymerization and the cleavage caused by the combination of antibodies and small molecules are all important factors affecting toxicity. (
  • Tomaszewski, J.E. Multi-species toxicology approaches for oncology drugs: the US perspective. (
  • In Immunotoxicity Testing: Methods and Protocols , expert researchers explore these changes, providing the reader with current, lab-ready procedures, along with the corresponding background information that is necessary to identify effective testing approaches for chemicals and drugs. (
  • Read on to learn what approaches scientists think might work to relieve COVID-19 symptoms, what drugs may cure serious cases, and other drugs that might prevent infection. (
  • Two recent reviews of the therapeutic use of antibodies suggest that systemically administered antibodies may play an important role in treating infections by drug-resistant pathogens as well as pathogens for which no antimicrobial drugs are available ( 2 , 3 ). (
  • Antiepileptic drugs can be grouped according to their major mechanism of action. (
  • Some antiepileptic drugs work by acting on combination of channels or through some unknown mechanism of action. (
  • With ongoing advancements in 3D cell technology, the potential for noninvasive, physiologically relevant (human), high-throughput drug screening and biomarker profiling is being realized. (
  • The main groups include sodium channel blockers, calcium current inhibitors, gamma-aminobutyric acid (GABA) enhancers, glutamate blockers, carbonic anhydrase inhibitors, hormones, and drugs with unknown mechanisms of action (see the image below). (
  • The claims of eight cisplatin analogues as viable alternatives to the parent drug are discussed in terms of their toxicities, antitumour properties and potential biochemical selectivities. (
  • Those parameters are important to guide the selection of a potential drug candidate and to determine future formulation strategies. (
  • The nature presented itself as a potential drug resource for scientists enabling serendipitous discoveries for centuries. (
  • Provided toxicological hazard evaluation of chemicals, such as those present in consumer products or the workplace, for the potential to cause skin or respiratory sensitization. (
  • Chemical validation of trypanothione synthetase: a potential drug target for human trypanosomiasis. (
  • a potential drug target for human trypanosomiasis . (
  • BACKGROUND: Recent work has developed solid drug nanoparticles (SDNs) of efavirenz that have been demonstrated, preclinically, improved oral bioavailability and the potential to enable up to a 50% dose reduction, and is currently being studied in a healthy volunteer clinical trial. (
  • Here we have conducted a preclinical evaluation of efavirenz SDN to assess their potential interaction with these systems. (
  • Nanodelivery carriers have the potential to maximise drug delivery to target cells. (
  • Known as ProgSTAR, the study has three primary goals: 1) Determine the best outcome measures to accelerate evaluation of emerging treatments in clinical trials, 2) better understand disease progression for selecting future clinical trial participants, and 3) identify potential participants for forthcoming clinical trials. (
  • According to PhRMA July 2013 Profile, for every 5,000 to 10,000 compounds that enter the drug pipeline, only one receives final approval. (
  • According to the FDA biopharmaceutics classification system (BCS), drug compounds can be classified into four classes based on their solubility and permeability (bioavailability). (
  • Neat compounds can be filled in bottles (drug in bottle) or into capsule (drug in capsule). (
  • Instead of delivering genes that express light-sensing proteins, their approach is to deliver light-sensing drugs (photoswitch compounds). (
  • The US Food and Drug Administration approved a 6-month regimen of pretomanid, bedaquiline, and linezolid for extensively drug-resistant or multidrug-intolerant tuberculosis after a trial in South Africa demonstrated 90% effectiveness 6 months posttreatment. (
  • On evaluation, the patient was asymptomatic without physical findings and reported no previous diagnosis or treatment of tuberculosis (TB) disease or latent TB infection. (