Genomes and Genes
preclinical drug evaluation
Summary: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.
Publications314 found, 100 shown here
- Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug developmentW S Redfern
Safety Assessment UK, AstraZeneca R and D Alderley Park, Macclesfield, Cheshire, UK
Cardiovasc Res 58:32-45. 2003..To attempt to determine the relative value of preclinical cardiac electrophysiology data (in vitro and in vivo) for predicting risk of torsade de pointes (TdP) in clinical use...
- Reaching for high-hanging fruit in drug discovery at protein-protein interfacesJames A Wells
Department of Pharmaceutical Chemistry, University of California at San Francisco, 1700 4th Street 503A, San Francisco, California 94156, USA
Nature 450:1001-9. 2007..Some of these small molecules are now making their way through clinical trials, so this high-hanging fruit might not be far out of reach...
- The many roles of computation in drug discoveryWilliam L Jorgensen
Department of Chemistry, Yale University, New Haven, CT 06520 8107, USA
Science 303:1813-8. 2004..Particular emphasis is placed on virtual screening, de novo design, evaluation of drug-likeness, and advanced methods for determining protein-ligand binding...
- Cell-based high-content screening of small-molecule librariesKerstin Korn
HT Technology Development Studio TDS, Max Planck Institute of Molecular Cell Biology and Genetics MPI CBG, Pfotenhauerstrasse 108, D 01307 Dresden, Germany
Curr Opin Chem Biol 11:503-10. 2007....
- Thrombopoietin protects against in vitro and in vivo cardiotoxicity induced by doxorubicinKaren Li
Department of Pediatrics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong
Circulation 113:2211-20. 2006..Our hypothesis is that the hematopoietic/megakaryocytopoietic growth factor thrombopoietin (TPO) protects against DOX-induced cardiotoxicity and might involve antiapoptotic mechanism exerted on cardiomyocytes...
- High-throughput and ultra-high-throughput screening: solution- and cell-based approachesS A Sundberg
Caliper Technologies Corporation, CA 94043, USA steve
Curr Opin Biotechnol 11:47-53. 2000..These devices provide orders-of-magnitude reduction in reagent consumption, and offer the potential for implementing high-throughput screening in formats that integrate up-front compound handling with unique assay functionality...
- High-throughput screening: new technology for the 21st centuryR P Hertzberg
Molecular Screening Technologies, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA
Curr Opin Chem Biol 4:445-51. 2000..Furthermore, new technologies are now being applied to information-rich cell-based assays, and this is beginning to remove one of the key bottlenecks downstream from primary screening...
- Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotesPek Yee Lum
Rosetta Inpharmatics LLC, a wholly owned subsidiary of Merck and Co, Inc, 12040 115th Avenue NE, Kirkland, WA 98034, USA
Cell 116:121-37. 2004....
- Multidimensional drug profiling by automated microscopyZachary E Perlman
Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Science 306:1194-8. 2004..Our methods will be useful for discovering the mechanism and predicting the toxicity of new drugs...
- Marine natural products and related compounds in clinical and advanced preclinical trialsDavid J Newman
Natural Products Branch, Developmental Therapeutics Program, NCI Frederick, P O Box B, Frederick, Maryland 21702, USA
J Nat Prod 67:1216-38. 2004..A substantial number of other potential agents are following in their wake in preclinical trials in these and in other diseases...
- Virtual screening of chemical librariesBrian K Shoichet
Department of Pharmaceutical Chemistry, University of California, 600 16th Street, San Francisco, California 94143 2240, USA
Nature 432:862-5. 2004....
- Preclinical pharmacokinetics: an approach towards safer and efficacious drugsSonu Sundd Singh
Nektar Therapeutics Private Limited, 1st Floor, 31 A, SD Road, Secunderabad, AP, India
Curr Drug Metab 7:165-82. 2006..HMD would provide an answer to the growing public demand for a reduction in the use of animals for pharmaceutical development...
- Induction of cyp1a1 is a nonspecific biomarker of aryl hydrocarbon receptor activation: results of large scale screening of pharmaceuticals and toxicants in vivo and in vitroWenyue Hu
Iconix Biosciences, Inc, 325 E Middlefield Road, Mountain View, CA 94043, USA
Mol Pharmacol 71:1475-86. 2007....
- Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell systemYoseph Shaaltiel
Protalix Biotherapeutics, 2 Snunit Street, Science Park, Carmiel 20100, Israel
Plant Biotechnol J 5:579-90. 2007..prGCD is currently undergoing clinical studies, and may offer a new and alternative therapeutic option for Gaucher's disease...
- Protein protein interaction inhibition (2P2I) combining high throughput and virtual screening: Application to the HIV-1 Nef proteinStephane Betzi
Bioénergétique et Ingénierie des Protéines Laboratory, Centre National de la Recherche Scientifique Institut de Biologie Structurale et Microbiologie, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France
Proc Natl Acad Sci U S A 104:19256-61. 2007....
- Recombinant green fluorescent protein-expressing human cytomegalovirus as a tool for screening antiviral agentsM Marschall
Institute of Clinical and Molecular Virology, University of Erlangen Nurnberg, Schlossgarten 4, 91054 Erlangen, Germany
Antimicrob Agents Chemother 44:1588-97. 2000....
- Cell-based assay for high-throughput quantitative screening of CFTR chloride transport agonistsL V Galietta
Department of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA
Am J Physiol Cell Physiol 281:C1734-42. 2001..The fluorescence assay and cell lines should facilitate the screening of novel CFTR activators and the characterization of alternative Cl(-) channels and transporters...
- Proof-of-principle: oncogenic beta-catenin is a valid molecular target for the development of pharmacological inhibitorsJung Sik Kim
Department of Oncology, Lombardi Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA
Mol Cancer Ther 1:1355-9. 2002....
- Development of a DNA vaccine designed to induce cytotoxic T lymphocyte responses to multiple conserved epitopes in HIV-1Cara C Wilson
University of Colorado Health Sciences Center, Denver, CO 80262, USA
J Immunol 171:5611-23. 2003..These data indicate that the EP HIV-1090 DNA vaccine may be suitable for inducing relevant HIV-1-specific CTL responses in humans...
- High-throughput assay for small molecules that modulate zebrafish embryonic heart rateC Geoffrey Burns
Developmental Biology Laboratory, Cardiovascular Research Center, Massachusetts General Hospital, 149 13th Street, Charlestown, Massachusetts 02129, USA
Nat Chem Biol 1:263-4. 2005..This is the first high-throughput micro-well assay for organ function in an intact vertebrate...
- Novel yeast cell-based assay to screen for inhibitors of human cytomegalovirus protease in a high-throughput formatValérie Cottier
ESBATech AG, Wagistr 21, CH 8952 Zurich Schlieren, Switzerland
Antimicrob Agents Chemother 50:565-71. 2006..The growth selection system presented here provides the basis for a high-throughput screen to identify HCMV protease inhibitors that are active in eukaryotic cells...
- Evaluating virtual screening methods: good and bad metrics for the "early recognition" problemJean Francois Truchon
Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, 16711 TransCanada Highway, Kirkland, Quebec, Canada H9H 3L1
J Chem Inf Model 47:488-508. 2007..Although this work is applied specifically to VS, it is general and can be used to analyze any method that needs to segregate actives toward the front of a rank-ordered list...
- Inhibition of angiogenesis by the antifungal drug itraconazoleCurtis R Chong
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
ACS Chem Biol 2:263-70. 2007..Together, these findings suggest that itraconazole has the potential to serve as an antiangiogenic drug and that lanosterol 14DM is a promising new target for discovering new angiogenesis inhibitors...
- A cell-based screen for drugs to treat Huntington's diseaseCharity T Aiken
Departments of Physiological Science and Neurology, Brain Research Institute, University of California, Los Angeles, CA 90095, USA
Neurobiol Dis 16:546-55. 2004..We believe these compounds, and others in our hit list, are appealing candidates for further investigation. Additionally, this assay is amenable to scaling up to screen additional compounds for treating Huntington's disease...
- Small molecule regulators of autophagy identified by an image-based high-throughput screenLihong Zhang
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China
Proc Natl Acad Sci U S A 104:19023-8. 2007..Our studies suggest the possibility that some of these drugs may be useful for the treatment of Huntington's and other human diseases associated with the accumulation of misfolded proteins...
- Antitumor activity of poly(L-glutamic acid)-paclitaxel on syngeneic and xenografted tumorsC Li
Division of Diagnostic Imaging, The University of Texas M D Anderson Cancer Center, Houston 77030, USA
Clin Cancer Res 5:891-7. 1999..Future studies to elucidate the mechanism of action of PG-TXL and to assess its clinical applications are warranted...
- Yeast and drug discoveryTimothy R Hughes
Banting and Best Department of Medical Research, University of Toronto, 112 College St, Toronto, ON M5G 1L6, Canada
Funct Integr Genomics 2:199-211. 2002..It is likely that most of the benefits of yeast in discovery and development of therapeutic compounds have yet to be realized...
- Anti-inflammatory and analgesic activities of mature fresh leaves of Vitex negundoM G Dharmasiri
Department of Zoology, University of Colombo, 3, Colombo, Sri Lanka
J Ethnopharmacol 87:199-206. 2003..The antihistamine activity can produce the anti-itching effect claimed in Ayurveda medicine...
- In vitro assays for evaluation of drug activity against Leishmania sppLuciana Fumarola
Department of Internal Medicine, Immunology and Infectious Diseases, Microbiology and Immunology Section, University of Bari, Medical School, Policlinico, Piazza Giulio Cesare, 70124 Bari, Italy
Res Microbiol 155:224-30. 2004..Reliable and simple in vitro models are required for large-scale initial screenings. In this review different methods for in vitro evaluation of drug activity against Leishmania spp. are summarized...
- Evaluation of fluorescence-based thermal shift assays for hit identification in drug discoveryMei Chu Lo
Biophysics Enzymology Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA
Anal Biochem 332:153-9. 2004..The potential pitfalls in the data analysis of thermal shift assays are also discussed...
- The use of zebrafish for assessing ototoxic and otoprotective agentsChristopher Ton
Phylonix Pharmaceuticals, Inc, 100 Inman St, Cambridge, MA 02139, USA
Hear Res 208:79-88. 2005..Our data indicate that results of ototoxicity and otoprotection in zebrafish correlated with results in humans, supporting use of zebrafish for preliminary drug screening...
- Drug discovery: playing dirtySimon Frantz
Nature 437:942-3. 2005
- The use of zebrafish to understand immunityNikolaus S Trede
Division of Pediatric Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115 USA
Immunity 20:367-79. 2004..Here, we discuss the advent of the zebrafish as a powerful vertebrate model organism that promises to positively impact immunologic research...
- Structure-based virtual screening: an overviewPaul D Lyne
AstraZeneca R and D Boston, Waltham, MA 02451, USA
Drug Discov Today 7:1047-55. 2002..Here, the current strengths and weaknesses of the technology are discussed, and emphasis is placed on aspects of the work-flow of a virtual screening campaign, from preparation through to post-screening analysis...
- Discovery of glycine hydrazide pore-occluding CFTR inhibitors: mechanism, structure-activity analysis, and in vivo efficacyChatchai Muanprasat
Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143 0521, USA
J Gen Physiol 124:125-37. 2004..Glycine hydrazides may be useful as probes of CFTR pore structure, in creating animal models of CF, and as antidiarrheals in enterotoxic-mediated secretory diarrheas...
- In vitro and in vivo influenza virus-inhibitory effects of viramidineRobert W Sidwell
Institute for Antiviral Research, Utah State University, Logan, UT 84322 5600, USA
Antiviral Res 68:10-7. 2005..While both compounds appear to have similar efficacy against influenza virus infections, when one considers the lesser toxicity, viramidine may warrant further evaluation as a possible therapy for influenza...
- Keynote review: in vitro safety pharmacology profiling: an essential tool for successful drug developmentSteven Whitebread
PreClinical Profiling, Lead Discovery Center, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA
Drug Discov Today 10:1421-33. 2005..In this article, we review the development of this tool for drug discovery, its appropriate use and predictive value...
- Identification of novel antimicrobials using a live-animal infection modelTerence I Moy
Department of Genetics, Harvard Medical School, Boston, MA 02114, USA
Proc Natl Acad Sci U S A 103:10414-9. 2006..Our findings indicate that the whole-animal C. elegans screen identifies not only traditional antibiotics, but also compounds that target bacterial virulence or stimulate host defense...
- A clinical drug library screen identifies astemizole as an antimalarial agentCurtis R Chong
Department of Pharmacology and Molecular Sciences The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nat Chem Biol 2:415-6. 2006..The antihistamine astemizole and its principal human metabolite are promising new inhibitors of chloroquine-sensitive and multidrug-resistant parasites, and they show efficacy in two mouse models of malaria...
- Discovery of trypanocidal compounds by whole cell HTS of Trypanosoma bruceiZachary B Mackey
Department of Pathology and the Sandler Center for Basic Research in Parasitic Diseases, University of California, QB3 1700 4th St, San Francisco, CA 94158, USA
Chem Biol Drug Des 67:355-63. 2006..These included the two approved trypanocidal drugs, suramin and pentamidine, several other drugs suspected but never validated as trypanocidal, and 17 novel trypanocidal drugs...
- High-affinity activators of cystic fibrosis transmembrane conductance regulator (CFTR) chloride conductance identified by high-throughput screeningTonghui Ma
Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
J Biol Chem 277:37235-41. 2002..The new activators identified here may be useful in defining molecular mechanisms of CFTR activation and as lead compounds in CF drug development...
- The significance of mitochondrial toxicity testing in drug developmentJames A Dykens
Drug Safety Research and Development, Pfizer Inc, 10646 Science Center Drive, San Diego, CA 92121, United States
Drug Discov Today 12:777-85. 2007....
- Novel inhibitors of poly(ADP-ribose) polymerase/PARP1 and PARP2 identified using a cell-based screen in yeastE Perkins
Iconix Pharmaceuticals, 320 Logue Avenue, Mountain View, CA 94043, USA
Cancer Res 61:4175-83. 2001..The resultant inhibitors have two critical uses (a) as leads for drug development and (b) as tools to dissect cellular function...
- Histidine-rich protein II: a novel approach to malaria drug sensitivity testingHarald Noedl
Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences USAMC AFRIMS, Bangkok, Thailand
Antimicrob Agents Chemother 46:1658-64. 2002..Standard operating procedures, updated information, and analytical software are available from http://malaria.farch.net...
- Development and application of fluorescence polarization assays in drug discoveryT J Burke
PanVera LLC, 501 Charmany Drive, Madison, WI 53719, USA
Comb Chem High Throughput Screen 6:183-94. 2003..These assays include targets such as kinases, phosphatases, proteases, G-protein coupled receptors, and nuclear receptors...
- Cardiovascular parameters in anaesthetized guinea pigs: a safety pharmacology screening modelDaniela S Hauser
Department of Pharmacology Gastroenterology, ALTANA Pharma AG, Byk Gulden Str 2, Constance 78467, Germany
J Pharmacol Toxicol Methods 52:106-14. 2005..The haemodynamic effects of repeated intravenous administrations of reference compounds were analyzed in order to validate the guinea pig model for safety pharmacology studies under GLP conditions...
- High-throughput assays for promiscuous inhibitorsBrian Y Feng
Department of Pharmaceutical Chemistry and Graduate Group in Chemistry and Chemical Biology, 1700 4th St, University of California San Francisco, San Francisco, California 94143 2550, USA
Nat Chem Biol 1:146-8. 2005..The results from these assays were used to test two preliminary computational models of this phenomenon and as benchmarks to develop new models...
- Selective optimization of side activities: the SOSA approachCamille G Wermuth
Prestwick Chemical, Boulevard Gonthier d Andernach, 67400 Illkirch, France
Drug Discov Today 11:160-4. 2006..This strategy has a high probability of yielding safe, bioavailable, original and patentable analogues...
- Inhibition profiling of human carbonic anhydrase II by high-throughput screening of structurally diverse, biologically active compoundsRema Iyer
Department of Biological Sciences, Western Michigan University, Kalamazoo, Michigan 49008 5410, USA
J Biomol Screen 11:782-91. 2006..Thus, this study yielded a number of potentially new classes of CA inhibitors and preliminary experiments to characterize their mechanism of action...
- Development of an in vivo rat screen model to predict pharmacokinetic interactions of CYP3A4 substratesS V Mandlekar
Pharmaceutical Candidate Optimization, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, USA
Xenobiotica 37:923-42. 2007..Based on the rank-order of interaction, the compounds could be prioritized for further preclinical development...
- Microfluidic gradient-generating device for pharmacological profilingJohan Pihl
Department of Chemistry and Bioscience, and Microtechnology Centre, Chalmers University of Technology, SE 412 96 Goteborg, Sweden
Anal Chem 77:3897-903. 2005..The device facilitates rapid pharmacological profiling of ion channel and GPCR effectors and enables the acquisition of large numbers of data points with minute sample consumption and handling...
- The discovery of a potent and selective lethal factor inhibitor for adjunct therapy of anthrax infectionYusheng Xiong
Merck Research Laboratories, Rahway, NJ 07065, USA
Bioorg Med Chem Lett 16:964-8. 2006..It has an IC50 of 54 nM in the enzyme assay and an IC50 of 210 nM in the macrophage cytotoxicity assay. Compound 40 is also effective in vivo in several animal model studies...
- Development of a new vaccine for the prevention of Lassa feverThomas W Geisbert
Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA
PLoS Med 2:e183. 2005..Currently, there are no licensed vaccines for Lassa fever, and no experimental vaccine has completely protected nonhuman primates against a lethal challenge...
- A small-molecule screen in C. elegans yields a new calcium channel antagonistTrevor C Y Kwok
Department of Medical Genetics and Microbiology, and The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada
Nature 441:91-5. 2006..Our study demonstrates that C. elegans enables rapid identification of new small-molecule tools and their targets...
- Teaching old drugs new tricks. Meeting of the Neurodegeneration Drug Screening Consortium, 7-8 April 2002, Washington, DC, USAJill Heemskerk
Technology Development Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
Trends Neurosci 25:494-6. 2002..Meeting of the Neurodegeneration Drug Screening Consortium, held on 7-8 April 2002, Washington, DC, USA...
- Improved statistical methods for hit selection in high-throughput screeningChristine Brideau
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada
J Biomol Screen 8:634-47. 2003..This system remotely processes HTS data using powerful and sophisticated statistical methodology but insulates users from the technical details by outputting results in a variety of readily interpretable graphs and tables...
- Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5Michael M Lederman
Department of Medicine, Case Western Reserve University, University Hospitals, 2061 Cornell Road, Cleveland, OH 44106, USA
Science 306:485-7. 2004..These experimental findings have potentially important implications for understanding vaginal transmission of HIV and the design of strategies for its prevention...
- Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylationStephen J Haggarty
Department of Molecular and Cellular Biology, and Harvard Institute of Chemistry and Cell Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
Proc Natl Acad Sci U S A 100:4389-94. 2003..They also suggest that small molecules that selectively inhibit HDAC6-mediated alpha-tubulin deacetylation, a first example of which is tubacin, might have therapeutic applications as antimetastatic and antiangiogenic agents...
- Preclinical evaluation of targeting the Nrf2 pathway by triterpenoids (CDDO-Im and CDDO-Me) for protection from LPS-induced inflammatory response and reactive oxygen species in human peripheral blood mononuclear cells and neutrophilsRajesh K Thimmulappa
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
Antioxid Redox Signal 9:1963-70. 2007....
- Genetic basis of individual differences in the response to small-molecule drugs in yeastEthan O Perlstein
Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Nat Genet 39:496-502. 2007..Our results provide a step toward a systematic understanding of small-molecule drug action in genetically distinct individuals...
- Mitogen-activated protein kinases in heart development and diseasesYibin Wang
Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
Circulation 116:1413-23. 2007..In this review, recent studies examining the role of MAP kinase subfamilies in cardiac development, hypertrophy, and survival are summarized...
- Target assessment for antiparasitic drug discoveryJulie A Frearson
Drug Discovery Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
Trends Parasitol 23:589-95. 2007..We hope this brief review will stimulate basic scientists to acquire additional information necessary for drug discovery...
- Neuroprotective agents for clinical trials in Parkinson's disease: a systematic assessmentB M Ravina
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Rockville, MD 20892 9257, USA
Neurology 60:1234-40. 2003..However, there have been relatively few clinical trials aimed at demonstrating neuroprotection. The authors sought to identify potential neuroprotective agents for testing in clinical trials...
- Stage-specific activity of potential antimalarial compounds measured in vitro by flow cytometry in comparison to optical microscopy and hypoxanthine uptakeCarmen E Contreras
Instituto de Inmunologia, Facultad de Medicina, Universidad Central, Apartado Postal 50109, Caracas 1050 A, Venezuela
Mem Inst Oswaldo Cruz 99:179-84. 2004..Advantages of flow cytometry analysis over traditional assays included higher throughput for data collection, insight into the stage-specificity of antimalarial activity avoiding use of radioactive isotopes...
- A human colorectal explant culture to evaluate topical microbicides for the prevention of HIV infectionSheila R Abner
HIV and Retrovirology Branch, Division of HIV AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, and Surgical Service, Emory University School of Medicine, Decatur, Georgia, USA
J Infect Dis 192:1545-56. 2005..These results suggest that this model is useful for evaluating the safety and efficacy of topical microbicides when used rectally...
- Utility of animal models for identification of potential therapeutics for rheumatoid arthritisM Hegen
Inflammation Discovery Research, Wyeth Research, Cambridge, MA 02140 2311, USA
Ann Rheum Dis 67:1505-15. 2008....
- N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activityNiels H Jensen
Department of Pharmacology, University of North Carolina Medical School, Chapel Hill, NC 27599, USA
Neuropsychopharmacology 33:2303-12. 2008..Possible contributions of this metabolite to the side effects of quetiapine are discussed...
- A novel high-throughput screening system identifies a small molecule repressive for matrix metalloproteinase-9 expressionRajesh R Nair
Center for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Ave, Albany, NY 12208, USA
Mol Pharmacol 73:919-29. 2008....
- Receptor-based virtual ligand screening for the identification of novel CDC25 phosphatase inhibitorsMatthieu Montes
UFR Biomedicale, Laboratoire de Pharmacochimie Moleculaire et Cellulaire, Universite Paris Descartes, Paris, F 75006, France
J Chem Inf Model 48:157-65. 2008..Our best compounds represent promising new classes of CDC25 inhibitors that also exhibit antiproliferative properties...
- Strategic approaches to developing drug treatments for ALSAndrea M Vincent
Department of Neurology, University of Michigan, Ann Arbor 48109, United States
Drug Discov Today 13:67-72. 2008..We review recent progress in promoting therapeutics into clinical trials and highlight the value of moderate throughput screening for the acceleration and improvement of drug design...
- Ex Vivo Metrics, a preclinical tool in new drug developmentC Gerald Curtis
J Transl Med 6:5. 2008..Early application of this tool for evaluating drug targeting, efficacy, and toxicity could result in better selection among promising drug candidates, greater drug productivity, and increased safety...
- In vitro trypanocidal activity of the anti-helminthic drug niclosamideKarin Merschjohann
Department of Parasitology, Ruprecht Karls University, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
Exp Parasitol 118:637-40. 2008..b. brucei and T. congolense, respectively. The very low toxicity of niclosamide for mammals makes the compound interesting for drug development for African trypanosomiasis...
- Discovery of potent pteridine reductase inhibitors to guide antiparasite drug developmentAntonio Cavazzuti
Dipartimento di Scienze Farmaceutiche, Universita di Modena e Reggio Emilia, Via Campi 183, 41100 Modena, Italy
Proc Natl Acad Sci U S A 105:1448-53. 2008..The successful combination of antifolates targeting two enzymes indicates high potential for such an approach in the development of previously undescribed antiparasitic drugs...
- Cellular mechanisms of growth inhibition of human endometrial cancer cell line by an antagonist of growth hormone-releasing hormoneLin Zhao
Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo 113 8655, Japan
Int J Oncol 32:593-601. 2008....
- Flexible ligand docking to multiple receptor conformations: a practical alternativeMaxim Totrov
Molsoft, 3366 N Torrey Pines Court, Suite 300, CA 92037, United States
Curr Opin Struct Biol 18:178-84. 2008..In several cases, such an approach has led to experimentally validated predictions...
- Comprehensive mechanistic analysis of hits from high-throughput and docking screens against beta-lactamaseKerim Babaoglu
Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California 94158 2330, USA
J Med Chem 51:2502-11. 2008..Structure-based methods may prioritize weak-but-novel chemotypes in unbiased library screens...
- Back to basics: label-free technologies for small molecule screeningAndrew K Shiau
Department of Biology, Kalypsys Inc, San Diego, CA 92121, USA
Comb Chem High Throughput Screen 11:231-7. 2008..The ultimate maturation of these techniques will enable drug discovery researchers to screen large chemical libraries against minimally manipulated biological systems...
- Rear-view mirrors and crystal balls: a brief reflection on drug discoveryJohn S Lazo
Mol Interv 8:60-3. 2008
- Recent developments in fragment-based drug discoveryMiles Congreve
Astex Therapeutics Ltd, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK
J Med Chem 51:3661-80. 2008
- Blocking cannabinoid CB1 receptors for the treatment of nicotine dependence: insights from pre-clinical and clinical studiesBernard Le Foll
Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada
Addict Biol 13:239-52. 2008..Rimonabant also appears to decrease relapse rates in smokers. These findings indicate significant, but limited, utility of rimonabant for smoking cessation...
- High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cellsSabrina C Desbordes
Developmental Biology Program, Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
Cell Stem Cell 2:602-12. 2008..The availability of high-content assays should accelerate progress in basic and translational hESC biology...
- Ensemble-based virtual screening reveals potential novel antiviral compounds for avian influenza neuraminidaseLily S Cheng
National Biomedical Computation Resource, University of California, San Diego, La Jolla, California 92093, USA
J Med Chem 51:3878-94. 2008..This ensemble-based VS and RCS approach may offer improvement over existing strategies for structure-based drug discovery...
- In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screenDavid Plouffe
Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA
Proc Natl Acad Sci U S A 105:9059-64. 2008..In addition, the screening method has the potential to provide the malaria community with many new starting points for the development of biological probes and drugs with novel antiparasitic activities...
- Single-bead, single-molecule, single-cell fluorescence: technologies for drug screening and target validationMartin Hintersteiner
Novartis Institutes for BioMedical Research, Innovative Screening Technologies, Brunner Strasse 59, A 1230 Vienna, Austria
Ann N Y Acad Sci 1130:1-11. 2008..The unlabeled small-molecular inhibitors represent chemical starting points in drug discovery and target validation...
- Drug target identification using side-effect similarityMonica Campillos
European Molecular Biology Laboratory EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Science 321:263-6. 2008..Nine of these were tested and confirmed in cell assays, documenting the feasibility of using phenotypic information to infer molecular interactions and hinting at new uses of marketed drugs...
- Molecular biology. Industrial-style screening meets academic biologyJocelyn Kaiser
Science 321:764-6. 2008
- Propidium iodide-based methods for monitoring drug action in the kinetoplastidae: comparison with the Alamar Blue assayMatthew K Gould
Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, 120 University Place, Glasgow G128TA, UK
Anal Biochem 382:87-93. 2008..The EC(50) values were highly similar to those obtained with the standard Alamar Blue assay. The procedure lends itself readily to applications in drug development or resistance monitoring...
- Computer-aided design and synthesis of nonpeptidic plasmepsin II and IV inhibitorsTorsten Luksch
Institut fur Pharmazeutische Chemie, Philipps Universitat Marburg, Marbacher Weg 6, 35032 Marburg, Germany
ChemMedChem 3:1323-36. 2008..The best-binding inhibitors designed for Plm II and IV are devoid of any inhibitory potency against human cathepsin D (EC number: 220.127.116.11)...
- Identification and characterization of small molecule inhibitors of Plasmodium falciparum dihydroorotate dehydrogenaseVishal Patel
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 283:35078-85. 2008..These data validate pfDHOD as an antimalarial drug target and provide chemical scaffolds with which to begin medicinal chemistry efforts...
- Identification of pharmacological chaperones for Gaucher disease and characterization of their effects on beta-glucocerebrosidase by hydrogen/deuterium exchange mass spectrometryMichael B Tropak
Research Institute, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G1X8, Canada
Chembiochem 9:2650-62. 2008....
- Development of a biological screening system for the evaluation of highly active and selective 17beta-HSD1-inhibitors as potential therapeutic agentsPatricia Kruchten
8 2 Pharmaceutical and Medicinal Chemistry, Saarland University, PO Box 15 11 50, D 66041 Saarbrucken, Germany
Mol Cell Endocrinol 301:154-7. 2009..Here, we report the development and application of our screening system using our in house library of potential 17beta-HSD1-inhibitors. Four potent and selective compounds with a good first pharmacokinetic profile were identified...
- Standardized high-throughput evaluation of cell-based compound screensPeter Frommolt
Institute of Medical Statistics, Informatics and Epidemiology, University of Koln, Koln, Germany
BMC Bioinformatics 9:475. 2008..Automation of the evaluation procedure and assessment of measurement accuracy can save time and improve the comparability of results...
- A robotic platform for quantitative high-throughput screeningSam Michael
NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20850, USA
Assay Drug Dev Technol 6:637-57. 2008..The combination of this system and qHTS has led to the generation of over 6 million CRCs from > 120 assays in the last 3 years and is a technology that can be widely implemented to increase efficiency of screening and lead generation...
- Type-II kinase inhibitor docking, screening, and profiling using modified structures of active kinase statesIrina Kufareva
The Scripps Research Institute, La Jolla, CA 92037, USA
J Med Chem 51:7921-32. 2008..Given the abundance of the DFG-in structures, the presented approach opens possibilities for kinome-wide discovery of specific molecules targeting inactive kinase states...
- Ligand-target prediction using Winnow and naive Bayesian algorithms and the implications of overall performance statisticsFlorian Nigsch
Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom
J Chem Inf Model 48:2313-25. 2008..This provided detailed information that can never be obtained by considering the overall performance statistics alone...
- Optimization and validation of two miniaturized glucocerebrosidase enzyme assays for high throughput screeningDaniel J Urban
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 3708, USA
Comb Chem High Throughput Screen 11:817-24. 2008..These two assays can be used to identify both GC activators and inhibitors with potential therapeutic value...
- A 96-well flow cytometric screening assay for detecting in vitro phospholipidosis-induction in the drug discovery phaseMesens Natalie
Global Preclinical Development, Johnson and Johnson Pharmaceutical Research and Development J and JPRD, 2340 Beerse, Belgium
Toxicol In Vitro 23:217-26. 2009..Based on an extended test set of reference compounds a profiling approach was introduced, by which we show we can rank our drug candidates according to their phospholipidosis-inducing potential...
- Mefloquine--an aminoalcohol with promising antischistosomal properties in miceJennifer Keiser
Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Basel, Switzerland
PLoS Negl Trop Dis 3:e350. 2009..Here, we report that the antimalarial drug mefloquine possesses promising antischistosomal properties in mice...
- A class of selective antibacterials derived from a protein kinase inhibitor pharmacophoreJ Richard Miller
Pfizer, Inc, Ann Arbor, MI 48105, USA
Proc Natl Acad Sci U S A 106:1737-42. 2009....
- Identification of three classes of heteroaromatic compounds with activity against intracellular Trypanosoma cruzi by chemical library screeningEsther Bettiol
Department of Medical Parasitology, New York University School of Medicine, New York, New York, United States of America
PLoS Negl Trop Dis 3:e384. 2009..These values are approximately 100 times lower than those of the medicines used in patients against T. cruzi. These results provide new candidate molecules for the development of treatments against Chagas disease and leishmaniasis...
- Efficient drug lead discovery and optimizationWilliam L Jorgensen
Department of Chemistry, Yale University, New Haven, Connecticut 06520 8107, USA
Acc Chem Res 42:724-33. 2009..Initial leads with activities at low-micromolar concentrations have been advanced rapidly to low-nanomolar inhibitors...
Research Grants118 found, 100 shown here
- Development of Natural Product as Antimalarial AgentShuren Zhu; Fiscal Year: 2007..Investigational new drug (IND) application will then be filed with FDA. [unreadable] [unreadable] [unreadable]..
- Kidney Multiphoton Analysis of Therapeutic AgentsKenneth Dunn; Fiscal Year: 2007..INphoton, LLC will commercialize multiphoton microscopy for preclinical drug evaluation in the kidney...
- Woo Young Lee; Fiscal Year: 2014..phenotype and mechanotransduction function of osteocytes for routine use in biomedical research and preclinical drug evaluation. We hypothesize that nanocomposite microbeads can be used to guide the re-establishment of 3D cellular ..
- Gerard Sanacora; Fiscal Year: 2014..potential to reveal altered glutamatergic/GABAergic neuronal and glial pathways, accelerating preclinical drug evaluation and treatment response...
- DISCOVERY AND DEVELOPMENT OF THERAPEUTIC COMPOUNDSJoseph McCune; Fiscal Year: 1993..Planned sessions will address a spectrum of issues, ranging from methods for preclinical drug evaluation in vitro and in vivo, to pharmacologic considerations necessary for preclinical and early clinical ..
- Nano-HPLC-ESI Quadrupole Ion Trap Mass SpectrometerAlan Smrcka; Fiscal Year: 2005..A cost recovery plan will be implemented that will cover costs in future years. ..
- TOTAL SYNTHESIS OF AZADIRACHTINK Nicolaou; Fiscal Year: 2008..The proposed work is expected to impact the general areas of pharmaceutical and agricultural research, and infectious diseases in particular, through discoveries in synthetic organic chemistry and chemical biology. ..
- Novel Delta Opioids: Analgesic Effects & Abuse LiabilitySIDNEY NEGUS; Fiscal Year: 2009....
- DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORSArun K Ghosh; Fiscal Year: 2010..This research integrates organic synthesis, protein-ligand x-ray crystallography, molecular modeling and in-depth virus and cell-biological studies to design the next generation of HIV-1 protease inhibitors. ..
- DEVELOPMENT OF LIGAND ASSISTED ASYMMETRIC SYNTHESESArun Ghosh; Fiscal Year: 2001..Besides the broad range of scope and generality, this line of research will provide excellent opportunities to teach and train graduate and undergraduate students in the laboratory. ..
- TOTAL SYNTHESIS OF NATURAL PRODUCTSK Nicolaou; Fiscal Year: 2002..3] sigmatropic rearrangement and a radical based ring closure to form the bicyclic skeleton. ..
- Pre-Clinical Development of Natural Product Analogues as Antimalarial AgentsShuren Zhu; Fiscal Year: 2007..Investigational new drug (IND) application will then be filed with FDA. Radix Pharmaceuticals has strategic alliance with commercial partners for Phase III development. [unreadable] [unreadable] [unreadable]..
- Improved Macaque Safety Model for Topical Microbicides: Post-coital AssessmentsDorothy Patton; Fiscal Year: 2008..In addition, we will collect parallel assessments, when mating has occurred with a placebo gel (HEC universal placebo) in place. These studies will provide urgently needed data regarding topical microbicide use with coital activity. ..
- LOCAL IMMUNE RESPONSE IN CHLAMYDIA SALPINGITISDorothy Patton; Fiscal Year: 2003..trachomatis- induced PID. If one chlamydial antigen is the major cause of the DTH response in PID, diagnostic or immunomodulatory efforts can be directed towards that antigen. ..
- SYNTHESIS OF ANTICANCER AGENTSK C Nicolaou; Fiscal Year: 2010..abstract_text> ..
- TOTAL SYNTHESIS OF APOPTOLIDINK Nicolaou; Fiscal Year: 2004..The proposed work is expected to have significant impact in the area of cancer chemotherapy and should provide enabling technologies and tools for biology and medicine. ..
- Enabling Technologies for Combinatorial ChemistryK Nicolaou; Fiscal Year: 2005..abstract_text> ..
- Effects of Probiotic Lactobacilli on Rotavirus ImmunityLijuan Yuan; Fiscal Year: 2006..The findings from this study will also facilitate an understanding of the potential adjuvant effects of probiotics for development of more effective vaccines against rotavirus and other enteric virus-induced diseases. ..
- STRUCTURAL BASIS FOR BINDING TO G PROTEIN BETA GAMMAAlan Smrcka; Fiscal Year: 2007..4. Identification of sites of interaction G protein betagamma subunits with cellular targets using deuterium exchange mass spectrometry. ..
- FUNCTIONAL ANALYSIS OF NF2 GENE MUTATIONSDavid Gutmann; Fiscal Year: 2003..Our ability to design rational therapies for schwannomas and meningiomas is dependent on an improved understanding of the mechanisms by which loss of merlin expression and function promotes tumor formation. ..
- HIV FRAMESHIFTING--FROM BIOLOGY TO THERAPEUTICSSTUART PELTZ; Fiscal Year: 2003..Their long-term goal will be to develop compounds that affect frame-shifting to the point that proof of principle has been established and antiviral agents targeting this process will be subsequently developed for clinical use. ..
- IL-12 as an Adjuvant for a Melanoma Peptide VaccineJeffrey Weber; Fiscal Year: 2003..The results of those assays will be used to design randomized phase III trials for resected high risk melanoma and to develop strategies for overcoming antigen-specific unresponsiveness in melanoma patients. ..
- Point-of-Care Measurement of Glycated HemoglobinMARGO COHEN; Fiscal Year: 2004....
- RATIONAL DEVELOPMENT OF THYROID RECEPTOR ANTAGONISTSMaxim Totrov; Fiscal Year: 2004..abstract_text> ..
- New drugs for treatment of atrial fibrillationAntonio Lacerda; Fiscal Year: 2004..ChanTest believes that this drug will offer great relief to the many people who are debilitated by atrial fibrillation. ..
- Aminoglycoside Antivirals to Combat ArenavirusesJUAN DE LA TORRE; Fiscal Year: 2004..Emergence of resistant variants will be assessed based on production of infectious virus and intracellular levels of virus RNA synthesis during serial passages in the presence of aminoglycosides with anti-LCMV activity. ..
- VASCULAR DISEASE IN DIABETIC NEUROPATHYMark Yorek; Fiscal Year: 2003..In summary, these studies will provide us with a better understanding of the etiology of DN and improved treatments for preventing the diabetes-induced changes in vascular and neural function. ..
- Phase II Study of 44Gy from 131I-81C6 for CNS TumorsDavid Reardon; Fiscal Year: 2004..To further define the toxicity of this approach and Specific Aim 3.To determine the impact of this therapy on quality of life. ..
- Throughput Assay:Allosteric Potentiator of GluR (RMI)P Conn; Fiscal Year: 2004..This will provide the characterization needed to allow us to optimize this assay for use in future screens of larger compound libraries. ..
- DEVELOPING AND IMPROVING INSTITUTIONAL ANIMAL RESOURCESJANICE WAGNER; Fiscal Year: 2006..unreadable] [unreadable]..
- Role of the CRF2 Receptor in Ingestive BehaviorEric Zorrilla; Fiscal Year: 2005..The proposed studies will address these questions as well to understand better the role of the CRF2 receptor in feeding behavior. ..
- Vascularization of Tissue Engineered Skeletal MuscleHerman Vandenburgh; Fiscal Year: 2006..Successful completion of this project will allow the development of a reversible ex vivo gene therapy method to treat hemophilia A. [unreadable] [unreadable] [unreadable]..
- Identification of Borna Disease Virus Receptor ProteinsJUAN DE LA TORRE; Fiscal Year: 2006..G*/p56; 3) Determination of expression pattern of BDV candidate receptors in vivo. ..
- In Vitro Tissue Model of PsoriasisSeyoum Ayehunie; Fiscal Year: 2006..unreadable] [unreadable] [unreadable]..
- Chemokine Signaling and Colitis in Gia2 Deficient MiceRobert Edwards; Fiscal Year: 2006..This application has the support of outstanding mentors at two institutions, and funding of this application will foster Dr Edwards' continued development as a physician-scientist. ..
- Zebrafish Assay for Parkinson's Disease DrugsPETER EIMON; Fiscal Year: 2006..Drugs that protect neurons from damage may be useful for the treatment of Parkinson's disease. [unreadable] [unreadable] [unreadable]..
- Development automated assay-regulators insulin synthesisPatrick McDonough; Fiscal Year: 2006..unreadable] [unreadable] [unreadable]..
- NOVEL NONPEPTIDE LIGANDS FOR THE OPIOID RECEPTORSSubramaniam Ananthan; Fiscal Year: 2007..unreadable] [unreadable] [unreadable]..
- Identification and Preclinical Evaluation of New Brain Tumor TherapiesDavid Gutmann; Fiscal Year: 2007..unreadable] [unreadable] [unreadable]..
- OmpR and acid regulation of Escherichia coli fim genesWILLIAM SCHWAN; Fiscal Year: 2007..unreadable] [unreadable] [unreadable] [unreadable]..
- REVERSE GENETICS OF ARENAVIRUSESJUAN DE LA TORRE; Fiscal Year: 2007..We will use biochemical, genetics and functional assays to assess the relevance in Arenavirus biology of candidates initially identified by TAP/MS. ..
- Regulatory Roles for Vascular Peptidases in AngiogenesisRenata Pasqualini; Fiscal Year: 2008..The proposed experiments in this application may also lead to development of new therapeutic strategies for diseases with an angiogenic component such as cancer and retinopathies. ..
- Molecular Determinants of Neural Stem Cell FunctionDavid Gutmann; Fiscal Year: 2008..unreadable] [unreadable] [unreadable] [unreadable]..
- High Content Drug Screening with Cardiac TissueHerman Vandenburgh; Fiscal Year: 2008..unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
- Development of Selective Nanoporous Sorbents for Radionuclide DecorporationCharles Timchalk; Fiscal Year: 2008..abstract_text> ..
- VACCINES FOR PREVENTION OF EXPERIMENTAL CONGENITAL CMVMark Schleiss; Fiscal Year: 2009..We anticipate that these subunit vaccine studies in this small animal model will clarify which strategies may be of value for vaccination against congenital HCMV infection. ..
- RESIN-BASED REMINERALIZING CEMENTS AND COMPOSITESSABINE DICKENS; Fiscal Year: 2009..Completion of this research will lead to Ca- PO4 cements and composites with improved adhesion to dentin and improved strength for ART and the treatment of root caries. ..
- Tobacco Smoking, Nicotine and Negative Affect ReliefKenneth Perkins; Fiscal Year: 2009..In sum, this research will help address the fundamental question of why cigarette smoking is reinforcing. ..
- NOVEL PHARMACOTHERAPY FOR TREATMENT OF COCAINE ADDICTIONFrank Carroll; Fiscal Year: 2008..abstract_text> ..
- The elmiric acids: biologically active anandamide analogs.SUMNER HOWARD BURSTEIN; Fiscal Year: 2010..A promising use for these compounds would be as narcotic replacement agents. ..
- Non-Human primate models for human xenotransplantationMary K Kearns Jonker; Fiscal Year: 2010..These organs function for three to six months before the grafts are rejected by antibodies. This study will identify the genes that encode these antibodies and will test novel ways to prevent this antibody response. ..
- TRANSMISSION OF PNEUMOCYSTIS INFECTIONMelanie Cushion; Fiscal Year: 2001..These studies will result in a clearer understanding of the biology leading to infection with Pc and will provide a rational basis for clinical management and therapeutic intervention. ..
- NOVEL PROBES FOR IMMUNOPHILIN MEDIATED CELL CONTROLTADEUSZ MOLINSKI; Fiscal Year: 2001..5. To understand how modulation of the FKBP12/ryanodine receptor complex by bastadins influences cellular growth and differentiation using the BC3H1 cell line as model. ..
- NON PSYCHOACTIVE CANNABINOIDS WITH THERAPEUTIC POTENTIALSumner Burstein; Fiscal Year: 2002..abstract_text> ..
- HEART FAILURE--CALCIUM HOMEOSTASIS AND ENERGY RESERVEJUDITH GWATHMEY; Fiscal Year: 2002..abstract_text> ..
- TREATMENT OF NEGATIVE SYMPTOMS AND COGNITIVE IMPAIRMENTSDaniel Javitt; Fiscal Year: 2003..The study will provide new information on the efficacy of d-cycloserine and glycine for both persistent primary and secondary negative symptoms and its effect on cognitive functioning. ..
- MOLECULAR BIOLOGY OF BORNA DISEASE VIRUS (BDV)JUAN DE LA TORRE; Fiscal Year: 2004..Conditions required for reconstitution of BDV transcription and RNA replication by intracellular coexpression of BDV minigenome and BDV proteins from separated plasmids will be determined. ..
- IRON CHELATORS PREDICATED ON DESFERRITHIOCINRAYMOND BERGERON; Fiscal Year: 2004....
- Rational Development of TCF/Beta-Catenin AntagonistsMaxim Totrov; Fiscal Year: 2004....
- DIRECTLY MEASURED T CELL DYNAMICS IN HIV PATHOGENESISMarc Hellerstein; Fiscal Year: 2004..Results have potential relevance to HIV-1 pathogenesis and therapy and to vaccination strategies. ..
- Proteomics/Genomics of Opiate Analgesia and AddictionVivian Hook; Fiscal Year: 2004..Elucidation of distinct pathways will be significant, since it could allow future design of opiate drug regimens that provide effective analgesia, without the tolerance and dependence of addiction. ..
- Contrasting Properties of Integrin Cytoplasmic DomainsRenata Pasqualini; Fiscal Year: 2004..A better understanding of angiogenesis and new ways of manipulating such process in physiological and pathological situations may result from this work. ..
- Amine N-Oxygenation by FMO3 and FMO4John Cashman; Fiscal Year: 2005..Such fundamental information will be useful in the development of safer drugs, the prevention of adverse drug reactions and the protection of humans from disease. ..
- Effects of insulin on the mesoaccumbens dopamine systemNICHOLAS BELLO; Fiscal Year: 2005..Insulin's modulation of food-related dopamine release may serve to increase the positive effects of palatable foods to contribute to pathological overeating and diet-induced obesity. ..
- Serotonin, Drug Use and MDMA Induced DeficitsFREDERICK MOELLER; Fiscal Year: 2005..Specific Aim 3: To determine whether neurobehavioral deficits seen in heavy MDMA users are related to serotonergic function as measured by a mCPP neuroendocrine challenge in these subjects. ..
- INTEGRATED DNA SEQUENCING SYSTEMVivian Hook; Fiscal Year: 2002..abstract_text> ..
- Induced hypothermic arrest in traumatic shockHasan Alam; Fiscal Year: 2005..Sub aim 2: Develop and test methods and techniques that can facilitate the induction of hypothermic arrest in the setting of traumatic shock. ..
- In Vitro Matrix-Cell Interaction in Bioartificial MuscleHerman Vandenburgh; Fiscal Year: 2005..abstract_text> ..
- NEUROPHYSIOLOGICAL NMDA DYSFUNCTION IN SCHIZOPHRENIADaniel Javitt; Fiscal Year: 2006..The research will build upon studies currently supported by NIH research and career development awards to the candidate, and will permit the candidate to continue to devote >75 percent effort to research. ..
- Topomer selection by chemists from All structuresRichard Cramer; Fiscal Year: 2006..abstract_text> ..
- Role of Cytokines in Two Hit Organ InjuryJean Nemzek; Fiscal Year: 2006..Successful completion of these aims could impact current two hit theories and use of immune therapy in septic patients exposed to additional inflammatory insults. ..
- Novel Smallpox Vaccine Derived from VV/VAR ImmunomeAnne De Groot; Fiscal Year: 2006..unreadable] [unreadable]..
- Advances in Mineral Metabolism (AMM) meetingRene St Arnaud; Fiscal Year: 2006..unreadable] [unreadable] [unreadable] [unreadable]..
- COMPLEX INVOLVED IN MRNA DECAY IN YEASTSTUART PELTZ; Fiscal Year: 2006..The goal is to amass a set of AU-rich elements large enough to facilitate computer analysis of the sequences to identify commonalities between them that might specify the proteins they interact with and their regulation. ..
- BEHAVIORAL EFFECTS AND ABUSE OF DOPAMINERGIC DRUGSJack Bergman; Fiscal Year: 2007..This research should point to novel directions for the development of medications with which to manage the abuse and addictive liabilities of psychomotor stimulant drugs ..
- Antifolate Resistance in OsteosarcomaRichard Gorlick; Fiscal Year: 2007....
- Biosynthesis of the Antibiotic Polyketide EnterocinBRADLEY MOORE; Fiscal Year: 2005..abstract_text> ..
- Neuroimmunologic Disorders Induced by Chronic Viral InfectionJUAN DE LA TORRE; Fiscal Year: 2007..unreadable] [unreadable] [unreadable]..
- MECHANISMS OF CANNABINOID'S ANTIEMETIC ACTIONSNISSAR DARMANI; Fiscal Year: 2007..The results will have important implications for the therapeutic utility of these "agonist antiemetics". [unreadable] [unreadable]..
- Technology and Endothelial Biology of Kidney Injury Molecule-1Vishal Vaidya; Fiscal Year: 2007..unreadable] [unreadable]..
- LDL Modification in Diabetic ComplicationsMARGO COHEN; Fiscal Year: 2007..unreadable] [unreadable] [unreadable]..
- Z-Tag for Measuring Cardiac Contractility and Cardiac RhythmicityPETER EIMON; Fiscal Year: 2007..Development of these assays will allow high-throughput, in vivo testing of drugs in development for cardiac toxicity. [unreadable] [unreadable] [unreadable]..
- Algorithm for drug discoveryGREGORY ELMER; Fiscal Year: 2007..Second, it will establish a core database for data mining and provide a template for use in screening novel compounds with potential clinical efficacy. [unreadable] [unreadable] [unreadable]..
- Curcumin-based analogs as improved inhibitors of Abeta aggregationROBERT ORLANDO; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- Central Mechanisms of Opiate Reinforcement and DependenceGeorge Koob; Fiscal Year: 2008....
- Adult human skeletal muscle stem cells for functional repairHerman Vandenburgh; Fiscal Year: 2008..unreadable] [unreadable] [unreadable] [unreadable]..
- CTLA-4 Inhibition and Autoimmunity in MelanomaJeffrey Weber; Fiscal Year: 2008..abstract_text> ..
- ANTIFUNGALS FROM MARINE INVERTEBRATES--AIDS ADJUVANTSTadeusz F Molinski; Fiscal Year: 2010..Optimized leads identified from those libraries will be advanced to in vitro and in vivo trials. ..
- Immune cell dynamics during central nervous system viral infectionJuan C de la Torre; Fiscal Year: 2010..abstract_text> ..
- Mechanisms of Neuronal Regeneration after Stroke in a Novel Neurovascular NicheSTANLEY THOMAS CARMICHAEL; Fiscal Year: 2010..An understanding of the molecules that promote this neural stem cell response after stroke will help develop novel therapies to promote replacement of brain cells in this disease. ..
- Legionella pneumophila developmental cycle & virulencePAUL STOKES HOFFMAN; Fiscal Year: 2011..These studies should also provide insights relevant to other opportunistic environmental pathogens including oxiella, Burkholderia and species of Mycobacterium. ..
- TARGETED DELIVERY OF GENES TO ANGIOGENIC VASCULATURERenata Pasqualini; Fiscal Year: 2004..Given that our peptides also target angiogenic vasculature in the retina, these advances are also likely to extend the potential for neovasculature-specific gene therapy targeting to other diseases involving angiogenesis. ..
- Cell Cycle and COX-2 in a Mouse Model of Alzheimer'sGiulio Pasinetti; Fiscal Year: 2004....
- INNOVATIVE BIOMONITORING FOR LEAD IN SALIVACharles Timchalk; Fiscal Year: 2006..It is reasonable to speculate that once this model system has been adequately validated it can readily be employed to screen sensitive populations (e.g. children) that are at greatest risk from chronic Pb exposure. ..
- Pinitol a Natural Extract from Pine Cones and Alzheimer's DiseaseGiulio Pasinetti; Fiscal Year: 2006..abstract_text> ..
- CELL SURFACE ACTIVITIES IN LIPOPROTEIN CATABOLISMROBERT ORLANDO; Fiscal Year: 2003....
- HPV DNA VACCINE FOR CERVICAL PRE NEOPLASIAJeffrey Weber; Fiscal Year: 2003..To insure that spontaneous regression does not account for a portion of the responses, baseline measurements will be followed one month later by a second set of assessments prior to the start of the vaccine. ..
- DEVELOPMENT OF SELECTIVE NICOTINIC RECEPTOR ANTAGONISTSLinda Dwoskin; Fiscal Year: 2001..These subtype selective nicotinic receptor antagonists would be invaluable neuropharmacological agents for basic and clinical research. ..
- HIV 1 TATS PROMOTION OF KAPOSIS SARCOMAFelipe Samaniego; Fiscal Year: 2002....
- DEVELOPMENT OF SELECTIVE NICOTINIC RECEPTOR ANTAGONISTSLinda Dwoskin; Fiscal Year: 2003..abstract_text> ..