preclinical drug evaluation

Summary

Summary: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.

Top Publications

  1. ncbi 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 development
    W S Redfern
    Safety Assessment UK, AstraZeneca R and D Alderley Park, Macclesfield, Cheshire, UK
    Cardiovasc Res 58:32-45. 2003
  2. ncbi Reaching for high-hanging fruit in drug discovery at protein-protein interfaces
    James 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
  3. ncbi The many roles of computation in drug discovery
    William L Jorgensen
    Department of Chemistry, Yale University, New Haven, CT 06520 8107, USA
    Science 303:1813-8. 2004
  4. ncbi Cell-based high-content screening of small-molecule libraries
    Kerstin 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
  5. ncbi Thrombopoietin protects against in vitro and in vivo cardiotoxicity induced by doxorubicin
    Karen Li
    Department of Pediatrics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong
    Circulation 113:2211-20. 2006
  6. ncbi High-throughput and ultra-high-throughput screening: solution- and cell-based approaches
    S A Sundberg
    Caliper Technologies Corporation, CA 94043, USA steve
    Curr Opin Biotechnol 11:47-53. 2000
  7. ncbi High-throughput screening: new technology for the 21st century
    R P Hertzberg
    Molecular Screening Technologies, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA
    Curr Opin Chem Biol 4:445-51. 2000
  8. ncbi Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes
    Pek 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
  9. ncbi Multidimensional drug profiling by automated microscopy
    Zachary E Perlman
    Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 306:1194-8. 2004
  10. ncbi Marine natural products and related compounds in clinical and advanced preclinical trials
    David 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

Research Grants

  1. Development of Natural Product as Antimalarial Agent
    Shuren Zhu; Fiscal Year: 2007
  2. Kidney Multiphoton Analysis of Therapeutic Agents
    Kenneth Dunn; Fiscal Year: 2007
  3. Woo Young Lee; Fiscal Year: 2014
  4. Gerard Sanacora; Fiscal Year: 2014
  5. DISCOVERY AND DEVELOPMENT OF THERAPEUTIC COMPOUNDS
    Joseph McCune; Fiscal Year: 1993
  6. Nano-HPLC-ESI Quadrupole Ion Trap Mass Spectrometer
    Alan Smrcka; Fiscal Year: 2005
  7. TOTAL SYNTHESIS OF AZADIRACHTIN
    K Nicolaou; Fiscal Year: 2008
  8. Novel Delta Opioids: Analgesic Effects & Abuse Liability
    SIDNEY NEGUS; Fiscal Year: 2009
  9. DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORS
    Arun K Ghosh; Fiscal Year: 2010
  10. DEVELOPMENT OF LIGAND ASSISTED ASYMMETRIC SYNTHESES
    Arun Ghosh; Fiscal Year: 2001

Detail Information

Publications314 found, 100 shown here

  1. ncbi 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 development
    W 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...
  2. ncbi Reaching for high-hanging fruit in drug discovery at protein-protein interfaces
    James 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...
  3. ncbi The many roles of computation in drug discovery
    William 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...
  4. ncbi Cell-based high-content screening of small-molecule libraries
    Kerstin 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
    ....
  5. ncbi Thrombopoietin protects against in vitro and in vivo cardiotoxicity induced by doxorubicin
    Karen 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...
  6. ncbi High-throughput and ultra-high-throughput screening: solution- and cell-based approaches
    S 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...
  7. ncbi High-throughput screening: new technology for the 21st century
    R 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...
  8. ncbi Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes
    Pek 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
    ....
  9. ncbi Multidimensional drug profiling by automated microscopy
    Zachary 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...
  10. ncbi Marine natural products and related compounds in clinical and advanced preclinical trials
    David 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...
  11. pmc Virtual screening of chemical libraries
    Brian K Shoichet
    Department of Pharmaceutical Chemistry, University of California, 600 16th Street, San Francisco, California 94143 2240, USA
    Nature 432:862-5. 2004
    ....
  12. ncbi Preclinical pharmacokinetics: an approach towards safer and efficacious drugs
    Sonu 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...
  13. pmc 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 vitro
    Wenyue Hu
    Iconix Biosciences, Inc, 325 E Middlefield Road, Mountain View, CA 94043, USA
    Mol Pharmacol 71:1475-86. 2007
    ....
  14. ncbi Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system
    Yoseph 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...
  15. pmc Protein protein interaction inhibition (2P2I) combining high throughput and virtual screening: Application to the HIV-1 Nef protein
    Stephane 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
    ....
  16. pmc Recombinant green fluorescent protein-expressing human cytomegalovirus as a tool for screening antiviral agents
    M Marschall
    Institute of Clinical and Molecular Virology, University of Erlangen Nurnberg, Schlossgarten 4, 91054 Erlangen, Germany
    Antimicrob Agents Chemother 44:1588-97. 2000
    ....
  17. ncbi Cell-based assay for high-throughput quantitative screening of CFTR chloride transport agonists
    L 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...
  18. ncbi Proof-of-principle: oncogenic beta-catenin is a valid molecular target for the development of pharmacological inhibitors
    Jung Sik Kim
    Department of Oncology, Lombardi Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA
    Mol Cancer Ther 1:1355-9. 2002
    ....
  19. ncbi Development of a DNA vaccine designed to induce cytotoxic T lymphocyte responses to multiple conserved epitopes in HIV-1
    Cara 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...
  20. ncbi High-throughput assay for small molecules that modulate zebrafish embryonic heart rate
    C 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...
  21. pmc Novel yeast cell-based assay to screen for inhibitors of human cytomegalovirus protease in a high-throughput format
    Valérie 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...
  22. ncbi Evaluating virtual screening methods: good and bad metrics for the "early recognition" problem
    Jean 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...
  23. ncbi Inhibition of angiogenesis by the antifungal drug itraconazole
    Curtis 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...
  24. ncbi A cell-based screen for drugs to treat Huntington's disease
    Charity 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...
  25. pmc Small molecule regulators of autophagy identified by an image-based high-throughput screen
    Lihong 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...
  26. ncbi Antitumor activity of poly(L-glutamic acid)-paclitaxel on syngeneic and xenografted tumors
    C 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...
  27. ncbi Yeast and drug discovery
    Timothy 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...
  28. ncbi Anti-inflammatory and analgesic activities of mature fresh leaves of Vitex negundo
    M 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...
  29. ncbi In vitro assays for evaluation of drug activity against Leishmania spp
    Luciana 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...
  30. ncbi Evaluation of fluorescence-based thermal shift assays for hit identification in drug discovery
    Mei 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...
  31. ncbi The use of zebrafish for assessing ototoxic and otoprotective agents
    Christopher 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...
  32. ncbi Drug discovery: playing dirty
    Simon Frantz
    Nature 437:942-3. 2005
  33. ncbi The use of zebrafish to understand immunity
    Nikolaus 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...
  34. ncbi Structure-based virtual screening: an overview
    Paul 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...
  35. pmc Discovery of glycine hydrazide pore-occluding CFTR inhibitors: mechanism, structure-activity analysis, and in vivo efficacy
    Chatchai 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...
  36. ncbi In vitro and in vivo influenza virus-inhibitory effects of viramidine
    Robert 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...
  37. ncbi Keynote review: in vitro safety pharmacology profiling: an essential tool for successful drug development
    Steven 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...
  38. pmc Identification of novel antimicrobials using a live-animal infection model
    Terence 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...
  39. ncbi A clinical drug library screen identifies astemizole as an antimalarial agent
    Curtis 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...
  40. ncbi Discovery of trypanocidal compounds by whole cell HTS of Trypanosoma brucei
    Zachary 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...
  41. ncbi High-affinity activators of cystic fibrosis transmembrane conductance regulator (CFTR) chloride conductance identified by high-throughput screening
    Tonghui 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...
  42. ncbi The significance of mitochondrial toxicity testing in drug development
    James 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
    ....
  43. ncbi Novel inhibitors of poly(ADP-ribose) polymerase/PARP1 and PARP2 identified using a cell-based screen in yeast
    E 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...
  44. pmc Histidine-rich protein II: a novel approach to malaria drug sensitivity testing
    Harald 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...
  45. ncbi Development and application of fluorescence polarization assays in drug discovery
    T 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...
  46. ncbi Cardiovascular parameters in anaesthetized guinea pigs: a safety pharmacology screening model
    Daniela 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...
  47. ncbi High-throughput assays for promiscuous inhibitors
    Brian 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...
  48. ncbi Selective optimization of side activities: the SOSA approach
    Camille 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...
  49. ncbi Inhibition profiling of human carbonic anhydrase II by high-throughput screening of structurally diverse, biologically active compounds
    Rema 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...
  50. ncbi Development of an in vivo rat screen model to predict pharmacokinetic interactions of CYP3A4 substrates
    S 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...
  51. ncbi Microfluidic gradient-generating device for pharmacological profiling
    Johan 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...
  52. ncbi The discovery of a potent and selective lethal factor inhibitor for adjunct therapy of anthrax infection
    Yusheng 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...
  53. pmc Development of a new vaccine for the prevention of Lassa fever
    Thomas 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...
  54. ncbi A small-molecule screen in C. elegans yields a new calcium channel antagonist
    Trevor 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...
  55. ncbi Teaching old drugs new tricks. Meeting of the Neurodegeneration Drug Screening Consortium, 7-8 April 2002, Washington, DC, USA
    Jill 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...
  56. ncbi Improved statistical methods for hit selection in high-throughput screening
    Christine 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...
  57. ncbi Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5
    Michael 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...
  58. pmc Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation
    Stephen 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...
  59. pmc 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 neutrophils
    Rajesh 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
    ....
  60. ncbi Genetic basis of individual differences in the response to small-molecule drugs in yeast
    Ethan 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...
  61. pmc Mitogen-activated protein kinases in heart development and diseases
    Yibin 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...
  62. pmc Target assessment for antiparasitic drug discovery
    Julie 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...
  63. ncbi Neuroprotective agents for clinical trials in Parkinson's disease: a systematic assessment
    B 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...
  64. ncbi Stage-specific activity of potential antimalarial compounds measured in vitro by flow cytometry in comparison to optical microscopy and hypoxanthine uptake
    Carmen 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...
  65. ncbi A human colorectal explant culture to evaluate topical microbicides for the prevention of HIV infection
    Sheila 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...
  66. ncbi Utility of animal models for identification of potential therapeutics for rheumatoid arthritis
    M Hegen
    Inflammation Discovery Research, Wyeth Research, Cambridge, MA 02140 2311, USA
    Ann Rheum Dis 67:1505-15. 2008
    ....
  67. ncbi N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity
    Niels 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...
  68. ncbi A novel high-throughput screening system identifies a small molecule repressive for matrix metalloproteinase-9 expression
    Rajesh 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
    ....
  69. ncbi Receptor-based virtual ligand screening for the identification of novel CDC25 phosphatase inhibitors
    Matthieu 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...
  70. pmc Strategic approaches to developing drug treatments for ALS
    Andrea 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...
  71. pmc Ex Vivo Metrics, a preclinical tool in new drug development
    C 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...
  72. doi In vitro trypanocidal activity of the anti-helminthic drug niclosamide
    Karin 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...
  73. pmc Discovery of potent pteridine reductase inhibitors to guide antiparasite drug development
    Antonio 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...
  74. ncbi Cellular mechanisms of growth inhibition of human endometrial cancer cell line by an antagonist of growth hormone-releasing hormone
    Lin Zhao
    Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo 113 8655, Japan
    Int J Oncol 32:593-601. 2008
    ....
  75. pmc Flexible ligand docking to multiple receptor conformations: a practical alternative
    Maxim 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...
  76. pmc Comprehensive mechanistic analysis of hits from high-throughput and docking screens against beta-lactamase
    Kerim 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...
  77. ncbi Back to basics: label-free technologies for small molecule screening
    Andrew 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...
  78. doi Rear-view mirrors and crystal balls: a brief reflection on drug discovery
    John S Lazo
    Mol Interv 8:60-3. 2008
  79. doi Recent developments in fragment-based drug discovery
    Miles Congreve
    Astex Therapeutics Ltd, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK
    J Med Chem 51:3661-80. 2008
  80. pmc Blocking cannabinoid CB1 receptors for the treatment of nicotine dependence: insights from pre-clinical and clinical studies
    Bernard 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...
  81. pmc High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cells
    Sabrina 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...
  82. pmc Ensemble-based virtual screening reveals potential novel antiviral compounds for avian influenza neuraminidase
    Lily 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...
  83. pmc In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen
    David 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...
  84. doi Single-bead, single-molecule, single-cell fluorescence: technologies for drug screening and target validation
    Martin 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...
  85. doi Drug target identification using side-effect similarity
    Monica 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...
  86. doi Molecular biology. Industrial-style screening meets academic biology
    Jocelyn Kaiser
    Science 321:764-6. 2008
  87. doi Propidium iodide-based methods for monitoring drug action in the kinetoplastidae: comparison with the Alamar Blue assay
    Matthew 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...
  88. doi Computer-aided design and synthesis of nonpeptidic plasmepsin II and IV inhibitors
    Torsten 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: 3.4.23.5)...
  89. pmc Identification and characterization of small molecule inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase
    Vishal 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...
  90. pmc Identification of pharmacological chaperones for Gaucher disease and characterization of their effects on beta-glucocerebrosidase by hydrogen/deuterium exchange mass spectrometry
    Michael B Tropak
    Research Institute, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G1X8, Canada
    Chembiochem 9:2650-62. 2008
    ....
  91. doi Development of a biological screening system for the evaluation of highly active and selective 17beta-HSD1-inhibitors as potential therapeutic agents
    Patricia 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...
  92. pmc Standardized high-throughput evaluation of cell-based compound screens
    Peter 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...
  93. pmc A robotic platform for quantitative high-throughput screening
    Sam 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...
  94. pmc Type-II kinase inhibitor docking, screening, and profiling using modified structures of active kinase states
    Irina 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...
  95. doi Ligand-target prediction using Winnow and naive Bayesian algorithms and the implications of overall performance statistics
    Florian 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...
  96. pmc Optimization and validation of two miniaturized glucocerebrosidase enzyme assays for high throughput screening
    Daniel 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...
  97. doi A 96-well flow cytometric screening assay for detecting in vitro phospholipidosis-induction in the drug discovery phase
    Mesens 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...
  98. pmc Mefloquine--an aminoalcohol with promising antischistosomal properties in mice
    Jennifer 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...
  99. pmc A class of selective antibacterials derived from a protein kinase inhibitor pharmacophore
    J Richard Miller
    Pfizer, Inc, Ann Arbor, MI 48105, USA
    Proc Natl Acad Sci U S A 106:1737-42. 2009
    ....
  100. pmc Identification of three classes of heteroaromatic compounds with activity against intracellular Trypanosoma cruzi by chemical library screening
    Esther 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...
  101. pmc Efficient drug lead discovery and optimization
    William 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

  1. Development of Natural Product as Antimalarial Agent
    Shuren Zhu; Fiscal Year: 2007
    ..Investigational new drug (IND) application will then be filed with FDA. [unreadable] [unreadable] [unreadable]..
  2. Kidney Multiphoton Analysis of Therapeutic Agents
    Kenneth Dunn; Fiscal Year: 2007
    ..INphoton, LLC will commercialize multiphoton microscopy for preclinical drug evaluation in the kidney...
  3. 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 ..
  4. Gerard Sanacora; Fiscal Year: 2014
    ..potential to reveal altered glutamatergic/GABAergic neuronal and glial pathways, accelerating preclinical drug evaluation and treatment response...
  5. DISCOVERY AND DEVELOPMENT OF THERAPEUTIC COMPOUNDS
    Joseph 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 ..
  6. Nano-HPLC-ESI Quadrupole Ion Trap Mass Spectrometer
    Alan Smrcka; Fiscal Year: 2005
    ..A cost recovery plan will be implemented that will cover costs in future years. ..
  7. TOTAL SYNTHESIS OF AZADIRACHTIN
    K 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. ..
  8. Novel Delta Opioids: Analgesic Effects & Abuse Liability
    SIDNEY NEGUS; Fiscal Year: 2009
    ....
  9. DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORS
    Arun 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. ..
  10. DEVELOPMENT OF LIGAND ASSISTED ASYMMETRIC SYNTHESES
    Arun 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. ..
  11. TOTAL SYNTHESIS OF NATURAL PRODUCTS
    K Nicolaou; Fiscal Year: 2002
    ..3] sigmatropic rearrangement and a radical based ring closure to form the bicyclic skeleton. ..
  12. Pre-Clinical Development of Natural Product Analogues as Antimalarial Agents
    Shuren 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]..
  13. Improved Macaque Safety Model for Topical Microbicides: Post-coital Assessments
    Dorothy 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. ..
  14. LOCAL IMMUNE RESPONSE IN CHLAMYDIA SALPINGITIS
    Dorothy 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. ..
  15. SYNTHESIS OF ANTICANCER AGENTS
    K C Nicolaou; Fiscal Year: 2010
    ..abstract_text> ..
  16. TOTAL SYNTHESIS OF APOPTOLIDIN
    K 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. ..
  17. Enabling Technologies for Combinatorial Chemistry
    K Nicolaou; Fiscal Year: 2005
    ..abstract_text> ..
  18. Effects of Probiotic Lactobacilli on Rotavirus Immunity
    Lijuan 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. ..
  19. STRUCTURAL BASIS FOR BINDING TO G PROTEIN BETA GAMMA
    Alan Smrcka; Fiscal Year: 2007
    ..4. Identification of sites of interaction G protein betagamma subunits with cellular targets using deuterium exchange mass spectrometry. ..
  20. FUNCTIONAL ANALYSIS OF NF2 GENE MUTATIONS
    David 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. ..
  21. HIV FRAMESHIFTING--FROM BIOLOGY TO THERAPEUTICS
    STUART 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. ..
  22. IL-12 as an Adjuvant for a Melanoma Peptide Vaccine
    Jeffrey 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. ..
  23. Point-of-Care Measurement of Glycated Hemoglobin
    MARGO COHEN; Fiscal Year: 2004
    ....
  24. RATIONAL DEVELOPMENT OF THYROID RECEPTOR ANTAGONISTS
    Maxim Totrov; Fiscal Year: 2004
    ..abstract_text> ..
  25. New drugs for treatment of atrial fibrillation
    Antonio Lacerda; Fiscal Year: 2004
    ..ChanTest believes that this drug will offer great relief to the many people who are debilitated by atrial fibrillation. ..
  26. Aminoglycoside Antivirals to Combat Arenaviruses
    JUAN 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. ..
  27. VASCULAR DISEASE IN DIABETIC NEUROPATHY
    Mark 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. ..
  28. Phase II Study of 44Gy from 131I-81C6 for CNS Tumors
    David 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. ..
  29. 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. ..
  30. DEVELOPING AND IMPROVING INSTITUTIONAL ANIMAL RESOURCES
    JANICE WAGNER; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  31. Role of the CRF2 Receptor in Ingestive Behavior
    Eric 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. ..
  32. Vascularization of Tissue Engineered Skeletal Muscle
    Herman 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]..
  33. Identification of Borna Disease Virus Receptor Proteins
    JUAN DE LA TORRE; Fiscal Year: 2006
    ..G*/p56; 3) Determination of expression pattern of BDV candidate receptors in vivo. ..
  34. In Vitro Tissue Model of Psoriasis
    Seyoum Ayehunie; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  35. Chemokine Signaling and Colitis in Gia2 Deficient Mice
    Robert 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. ..
  36. Zebrafish Assay for Parkinson's Disease Drugs
    PETER EIMON; Fiscal Year: 2006
    ..Drugs that protect neurons from damage may be useful for the treatment of Parkinson's disease. [unreadable] [unreadable] [unreadable]..
  37. Development automated assay-regulators insulin synthesis
    Patrick McDonough; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  38. NOVEL NONPEPTIDE LIGANDS FOR THE OPIOID RECEPTORS
    Subramaniam Ananthan; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  39. Identification and Preclinical Evaluation of New Brain Tumor Therapies
    David Gutmann; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  40. OmpR and acid regulation of Escherichia coli fim genes
    WILLIAM SCHWAN; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  41. REVERSE GENETICS OF ARENAVIRUSES
    JUAN 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. ..
  42. Regulatory Roles for Vascular Peptidases in Angiogenesis
    Renata 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. ..
  43. Molecular Determinants of Neural Stem Cell Function
    David Gutmann; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  44. High Content Drug Screening with Cardiac Tissue
    Herman Vandenburgh; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  45. Development of Selective Nanoporous Sorbents for Radionuclide Decorporation
    Charles Timchalk; Fiscal Year: 2008
    ..abstract_text> ..
  46. VACCINES FOR PREVENTION OF EXPERIMENTAL CONGENITAL CMV
    Mark 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. ..
  47. RESIN-BASED REMINERALIZING CEMENTS AND COMPOSITES
    SABINE 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. ..
  48. Tobacco Smoking, Nicotine and Negative Affect Relief
    Kenneth Perkins; Fiscal Year: 2009
    ..In sum, this research will help address the fundamental question of why cigarette smoking is reinforcing. ..
  49. NOVEL PHARMACOTHERAPY FOR TREATMENT OF COCAINE ADDICTION
    Frank Carroll; Fiscal Year: 2008
    ..abstract_text> ..
  50. 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. ..
  51. Non-Human primate models for human xenotransplantation
    Mary 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. ..
  52. TRANSMISSION OF PNEUMOCYSTIS INFECTION
    Melanie 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. ..
  53. NOVEL PROBES FOR IMMUNOPHILIN MEDIATED CELL CONTROL
    TADEUSZ 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. ..
  54. NON PSYCHOACTIVE CANNABINOIDS WITH THERAPEUTIC POTENTIAL
    Sumner Burstein; Fiscal Year: 2002
    ..abstract_text> ..
  55. HEART FAILURE--CALCIUM HOMEOSTASIS AND ENERGY RESERVE
    JUDITH GWATHMEY; Fiscal Year: 2002
    ..abstract_text> ..
  56. TREATMENT OF NEGATIVE SYMPTOMS AND COGNITIVE IMPAIRMENTS
    Daniel 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. ..
  57. 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. ..
  58. IRON CHELATORS PREDICATED ON DESFERRITHIOCIN
    RAYMOND BERGERON; Fiscal Year: 2004
    ....
  59. Rational Development of TCF/Beta-Catenin Antagonists
    Maxim Totrov; Fiscal Year: 2004
    ....
  60. DIRECTLY MEASURED T CELL DYNAMICS IN HIV PATHOGENESIS
    Marc Hellerstein; Fiscal Year: 2004
    ..Results have potential relevance to HIV-1 pathogenesis and therapy and to vaccination strategies. ..
  61. Proteomics/Genomics of Opiate Analgesia and Addiction
    Vivian 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. ..
  62. Contrasting Properties of Integrin Cytoplasmic Domains
    Renata 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. ..
  63. Amine N-Oxygenation by FMO3 and FMO4
    John 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. ..
  64. Effects of insulin on the mesoaccumbens dopamine system
    NICHOLAS 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. ..
  65. Serotonin, Drug Use and MDMA Induced Deficits
    FREDERICK 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. ..
  66. INTEGRATED DNA SEQUENCING SYSTEM
    Vivian Hook; Fiscal Year: 2002
    ..abstract_text> ..
  67. Induced hypothermic arrest in traumatic shock
    Hasan 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. ..
  68. In Vitro Matrix-Cell Interaction in Bioartificial Muscle
    Herman Vandenburgh; Fiscal Year: 2005
    ..abstract_text> ..
  69. NEUROPHYSIOLOGICAL NMDA DYSFUNCTION IN SCHIZOPHRENIA
    Daniel 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. ..
  70. Topomer selection by chemists from All structures
    Richard Cramer; Fiscal Year: 2006
    ..abstract_text> ..
  71. Role of Cytokines in Two Hit Organ Injury
    Jean 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. ..
  72. Novel Smallpox Vaccine Derived from VV/VAR Immunome
    Anne De Groot; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  73. Advances in Mineral Metabolism (AMM) meeting
    Rene St Arnaud; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  74. COMPLEX INVOLVED IN MRNA DECAY IN YEAST
    STUART 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. ..
  75. BEHAVIORAL EFFECTS AND ABUSE OF DOPAMINERGIC DRUGS
    Jack 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 ..
  76. Antifolate Resistance in Osteosarcoma
    Richard Gorlick; Fiscal Year: 2007
    ....
  77. Biosynthesis of the Antibiotic Polyketide Enterocin
    BRADLEY MOORE; Fiscal Year: 2005
    ..abstract_text> ..
  78. Neuroimmunologic Disorders Induced by Chronic Viral Infection
    JUAN DE LA TORRE; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  79. MECHANISMS OF CANNABINOID'S ANTIEMETIC ACTIONS
    NISSAR DARMANI; Fiscal Year: 2007
    ..The results will have important implications for the therapeutic utility of these "agonist antiemetics". [unreadable] [unreadable]..
  80. Technology and Endothelial Biology of Kidney Injury Molecule-1
    Vishal Vaidya; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  81. LDL Modification in Diabetic Complications
    MARGO COHEN; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  82. Z-Tag for Measuring Cardiac Contractility and Cardiac Rhythmicity
    PETER 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]..
  83. Algorithm for drug discovery
    GREGORY 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]..
  84. Curcumin-based analogs as improved inhibitors of Abeta aggregation
    ROBERT ORLANDO; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  85. Central Mechanisms of Opiate Reinforcement and Dependence
    George Koob; Fiscal Year: 2008
    ....
  86. Adult human skeletal muscle stem cells for functional repair
    Herman Vandenburgh; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  87. CTLA-4 Inhibition and Autoimmunity in Melanoma
    Jeffrey Weber; Fiscal Year: 2008
    ..abstract_text> ..
  88. ANTIFUNGALS FROM MARINE INVERTEBRATES--AIDS ADJUVANTS
    Tadeusz F Molinski; Fiscal Year: 2010
    ..Optimized leads identified from those libraries will be advanced to in vitro and in vivo trials. ..
  89. Immune cell dynamics during central nervous system viral infection
    Juan C de la Torre; Fiscal Year: 2010
    ..abstract_text> ..
  90. Mechanisms of Neuronal Regeneration after Stroke in a Novel Neurovascular Niche
    STANLEY 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. ..
  91. Legionella pneumophila developmental cycle & virulence
    PAUL STOKES HOFFMAN; Fiscal Year: 2011
    ..These studies should also provide insights relevant to other opportunistic environmental pathogens including oxiella, Burkholderia and species of Mycobacterium. ..
  92. TARGETED DELIVERY OF GENES TO ANGIOGENIC VASCULATURE
    Renata 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. ..
  93. Cell Cycle and COX-2 in a Mouse Model of Alzheimer's
    Giulio Pasinetti; Fiscal Year: 2004
    ....
  94. INNOVATIVE BIOMONITORING FOR LEAD IN SALIVA
    Charles 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. ..
  95. Pinitol a Natural Extract from Pine Cones and Alzheimer's Disease
    Giulio Pasinetti; Fiscal Year: 2006
    ..abstract_text> ..
  96. CELL SURFACE ACTIVITIES IN LIPOPROTEIN CATABOLISM
    ROBERT ORLANDO; Fiscal Year: 2003
    ....
  97. HPV DNA VACCINE FOR CERVICAL PRE NEOPLASIA
    Jeffrey 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. ..
  98. DEVELOPMENT OF SELECTIVE NICOTINIC RECEPTOR ANTAGONISTS
    Linda Dwoskin; Fiscal Year: 2001
    ..These subtype selective nicotinic receptor antagonists would be invaluable neuropharmacological agents for basic and clinical research. ..
  99. HIV 1 TATS PROMOTION OF KAPOSIS SARCOMA
    Felipe Samaniego; Fiscal Year: 2002
    ....
  100. DEVELOPMENT OF SELECTIVE NICOTINIC RECEPTOR ANTAGONISTS
    Linda Dwoskin; Fiscal Year: 2003
    ..abstract_text> ..