Christopher P Austin

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening
    Naris Nilubol
    Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 10 Center Drive, MSC 1201, Bethesda, MD 20892, USA
    J Transl Med 10:198. 2012
  2. pmc The knockout mouse project
    Christopher P Austin
    National Human Genome Research Institute, National Institutes of Health, Building 31, Room 4B09, 31 Center Drive, Bethesda, Maryland 20892, USA
    Nat Genet 36:921-4. 2004
  3. ncbi request reprint NIH Molecular Libraries Initiative
    Christopher P Austin
    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Science 306:1138-9. 2004
  4. ncbi request reprint The impact of the completed human genome sequence on the development of novel therapeutics for human disease
    Christopher P Austin
    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Annu Rev Med 55:1-13. 2004
  5. ncbi request reprint The completed human genome: implications for chemical biology
    Christopher P Austin
    National Human Genome Research Institute, National Institutes of Health Building 31, Room 4B09, 31 Center Drive, Bethesda, MD 20892, USA
    Curr Opin Chem Biol 7:511-5. 2003
  6. pmc Application of a homogenous membrane potential assay to assess mitochondrial function
    Srilatha Sakamuru
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, Maryland 20892 3370, USA
    Physiol Genomics 44:495-503. 2012
  7. pmc High throughput screening for small molecule therapy for Gaucher disease using patient tissue as the source of mutant glucocerebrosidase
    Ehud Goldin
    Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 7:e29861. 2012
  8. 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
  9. pmc Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase
    Jian Kang Jiang
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, USA
    Bioorg Med Chem Lett 20:3387-93. 2010
  10. pmc A multiplex calcium assay for identification of GPCR agonists and antagonists
    Ke Liu
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
    Assay Drug Dev Technol 8:367-79. 2010

Collaborators

Detail Information

Publications88

  1. pmc Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening
    Naris Nilubol
    Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 10 Center Drive, MSC 1201, Bethesda, MD 20892, USA
    J Transl Med 10:198. 2012
    ..The objective of this study was to identify and validate drugs with antineoplastic effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique...
  2. pmc The knockout mouse project
    Christopher P Austin
    National Human Genome Research Institute, National Institutes of Health, Building 31, Room 4B09, 31 Center Drive, Bethesda, Maryland 20892, USA
    Nat Genet 36:921-4. 2004
    ..It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain...
  3. ncbi request reprint NIH Molecular Libraries Initiative
    Christopher P Austin
    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Science 306:1138-9. 2004
  4. ncbi request reprint The impact of the completed human genome sequence on the development of novel therapeutics for human disease
    Christopher P Austin
    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Annu Rev Med 55:1-13. 2004
    ..These improvements will require increased physician understanding of genetic principles applied to common diseases...
  5. ncbi request reprint The completed human genome: implications for chemical biology
    Christopher P Austin
    National Human Genome Research Institute, National Institutes of Health Building 31, Room 4B09, 31 Center Drive, Bethesda, MD 20892, USA
    Curr Opin Chem Biol 7:511-5. 2003
    ..Small-molecule chemical biology applied on a genomic scale promises to speed this translation to novel therapeutics...
  6. pmc Application of a homogenous membrane potential assay to assess mitochondrial function
    Srilatha Sakamuru
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, Maryland 20892 3370, USA
    Physiol Genomics 44:495-503. 2012
    ..Our results demonstrate that this homogenous cell-based Mito-MPS assay can be used to evaluate the ability of large numbers of chemicals to decrease mitochondrial function...
  7. pmc High throughput screening for small molecule therapy for Gaucher disease using patient tissue as the source of mutant glucocerebrosidase
    Ehud Goldin
    Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 7:e29861. 2012
    ..These results suggest that primary screening assays using enzyme extracted from tissues is an alternative approach to identify high quality, physiologically relevant lead compounds for drug development...
  8. 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...
  9. pmc Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase
    Jian Kang Jiang
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, USA
    Bioorg Med Chem Lett 20:3387-93. 2010
    ..These agents represent the second reported chemotype for activation of PKM2...
  10. pmc A multiplex calcium assay for identification of GPCR agonists and antagonists
    Ke Liu
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
    Assay Drug Dev Technol 8:367-79. 2010
    ..This multiplexed assay format provides an efficient and cost-effective method for HTS of G(q)-coupled GPCR targets...
  11. pmc A miniaturized glucocorticoid receptor translocation assay using enzymatic fragment complementation evaluated with qHTS
    Ping Jun Zhu
    National Institutes of Health, National Human Genome Research Institute, NIH Chemical Genomics Center, Bethesda, MD 20892 3370, USA
    Comb Chem High Throughput Screen 11:545-59. 2008
    ....
  12. pmc Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets
    Jing Yuan
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Science 333:724-9. 2011
    ..Drugs whose responses mapped to wild-type or mutant pfcrt alleles were tested in combination in vitro and in vivo, which yielded promising new leads for antimalarial treatments...
  13. pmc Structure mechanism insights and the role of nitric oxide donation guide the development of oxadiazole-2-oxides as therapeutic agents against schistosomiasis
    Ganesha Rai
    NIH Chemical Genomics Center, National Human Genome Research Institute, NIH, 9800 Medical Center Drive, MSC 3370, Bethesda, Maryland 20892 3370, USA
    J Med Chem 52:6474-83. 2009
    ..The results of these studies verify the utility of oxadiazole-2-oxides as novel inhibitors of TGR and as efficacious antischistosomal agents...
  14. pmc Evaluation of quinazoline analogues as glucocerebrosidase inhibitors with chaperone activity
    Juan J Marugan
    NIH Chemical Genomic Center, National Human Genome Research Institute, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland, United States
    J Med Chem 54:1033-58. 2011
    ....
  15. pmc Synthesis and characterization of a new fluorogenic substrate for alpha-galactosidase
    Zhen Dan Shi
    Imaging Probe Development Center, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 3708, USA
    Anal Bioanal Chem 394:1903-9. 2009
    ..Therefore, this new red fluorogenic substrate and the resulting enzyme assay can be used in high-throughput screening to identify small-molecule chaperones for Fabry disease...
  16. pmc Evaluation of substituted N,N'-diarylsulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase
    Matthew B Boxer
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, 9800 Medical Center Drive, MSC 3370 Bethesda, Maryland 20850, USA
    J Med Chem 53:1048-55. 2010
    ..7 microg/mL), and 58 (AC(50) = 38 nM, maximum response = 82%; solubility = 51.2 microg/mL). The small molecules described here represent first-in-class activators of PKM2...
  17. pmc Identification of compounds that potentiate CREB signaling as possible enhancers of long-term memory
    Menghang Xia
    NIH Chemical Genomics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:2412-7. 2009
    ..qHTS followed by interrogation of pathway targets is an efficient paradigm for lead generation for chemical genomics and drug development...
  18. pmc Small-molecule agonists for the thyrotropin receptor stimulate thyroid function in human thyrocytes and mice
    Susanne Neumann
    Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:12471-6. 2009
    ..Thus, we discovered a small molecule that activates human TSHR in vitro, is orally active in mice, and could be a lead for development of drugs to use in place of recombinant human TSH in patients with thyroid cancer...
  19. pmc A basis for reduced chemical library inhibition of firefly luciferase obtained from directed evolution
    Douglas S Auld
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, Maryland 20892 3370, USA
    J Med Chem 52:1450-8. 2009
    ..This study demonstrates the power of large-scale quantitative analysis of structure-activity relationships (>100K compounds) in addressing important questions such as a target's druggability...
  20. pmc A quantitative high-throughput screen identifies potential epigenetic modulators of gene expression
    Ronald L Johnson
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, MD 20892, USA
    Anal Biochem 375:237-48. 2008
    ..These results suggest that the identified small molecules act on epigenetic or transcriptional components and validate our approach of using a cell-based imaging assay in conjunction with qHTS...
  21. pmc Identification of small molecule compounds that inhibit the HIF-1 signaling pathway
    Menghang Xia
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Mol Cancer 8:117. 2009
    ..To identify small molecule inhibitors of the HIF-1 pathway, we have developed a cell-based reporter gene assay and screened a large compound library by using a quantitative high-throughput screening (qHTS) approach...
  22. pmc The pilot phase of the NIH Chemical Genomics Center
    Craig J Thomas
    NIH Chemical Genomics Center, NHGRI, National Institutes of Health, 9800 Medical Center Drive, Building B, Room 3005, MSC 3370, Bethesda, MD 20892 3370, USA
    Curr Top Med Chem 9:1181-93. 2009
    ....
  23. 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...
  24. pmc Evaluation of substituted 6-arylquinazolin-4-amines as potent and selective inhibitors of cdc2-like kinases (Clk)
    Bryan T Mott
    NIH Chemical Genomics Center, National Human Genome Research Institute, Bethesda, MD 20892 3370, USA
    Bioorg Med Chem Lett 19:6700-5. 2009
    ..Molecular docking provides further evidence that inhibition is the result of binding at the kinase hinge region. Selected compounds represent novel tools capable of potent and selective inhibition of Clk1, Clk4, and Dyrk1A...
  25. pmc Monitoring compound integrity with cytochrome P450 assays and qHTS
    Ryan MacArthur
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, MD 20892 3370, USA
    J Biomol Screen 14:538-46. 2009
    ..Furthermore, the study illustrates the degree and time scale of apparent compound potency changes due to sample storage...
  26. pmc Evaluation of 2-thioxo-2,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidin-4(1H)-one analogues as GAA activators
    Juan J Marugan
    NIH Chemical Genomic Center, National Human Genome Research Institute, National Institutes of Heath, 9800 Medical Center Drive, Rockville, MD, USA
    Eur J Med Chem 45:1880-97. 2010
    ..Herein we report our initial findings of a new series of acid alpha-glucosidase activators...
  27. pmc Characterization of diversity in toxicity mechanism using in vitro cytotoxicity assays in quantitative high throughput screening
    Ruili Huang
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, Maryland 20892 3370, USA
    Chem Res Toxicol 21:659-67. 2008
    ..The performance of this clustering method is evaluated by comparing the clustering results against literature annotations of compound mechanisms...
  28. pmc Quantitative high-throughput screen identifies inhibitors of the Schistosoma mansoni redox cascade
    Anton Simeonov
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Negl Trop Dis 2:e127. 2008
    ....
  29. pmc Identification and optimization of inhibitors of Trypanosomal cysteine proteases: cruzain, rhodesain, and TbCatB
    Bryan T Mott
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, 9800 Medical Center Drive, MSC 3370 Bethesda, Maryland 20892 3370, USA
    J Med Chem 53:52-60. 2010
    ..brucei parasites. Selected compounds were screened against a panel of human cysteine and serine proteases to determine selectivity, and a cocrystal was obtained of our most potent analogue bound to cruzain...
  30. pmc Quantitative analyses of aggregation, autofluorescence, and reactivity artifacts in a screen for inhibitors of a thiol protease
    Ajit Jadhav
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892 3370, USA
    J Med Chem 53:37-51. 2010
    ..The distribution of false positives was relatively constant across library sources. The simple step of including detergent in the assay buffer suppressed the nonspecific effect of approximately 93% of the original hits...
  31. pmc Exploration and optimization of substituted triazolothiadiazines and triazolopyridazines as PDE4 inhibitors
    Amanda P Skoumbourdis
    NIH Chemical Genomics Center, National Human Genome Research Institute, NIH 9800 Medical Center Drive, MSC 3370 Bethesda, MD 20892 3370, USA
    Bioorg Med Chem Lett 19:3686-92. 2009
    ..Finally, docking studies with selective ligands (including 10 and 18) were undertaken to better understand this chemotypes ability to bind and inhibit PDE4 selectively...
  32. doi request reprint Characterization of chemical libraries for luciferase inhibitory activity
    Douglas S Auld
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892 3370, USA
    J Med Chem 51:2372-86. 2008
    ..pyralis luciferase. We describe the structure-activity relationship of the luciferase inhibitors and discuss the use of this data in the interpretation of HTS results and configuration of luciferase-based assays...
  33. doi request reprint Fluorescence spectroscopic profiling of compound libraries
    Anton Simeonov
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892 3370, USA
    J Med Chem 51:2363-71. 2008
    ..Native compound fluorescence, fluorescent impurities, novel fluorescent compounds, and the utilization of fluorescence profiling data are discussed...
  34. pmc Identification of quaternary ammonium compounds as potent inhibitors of hERG potassium channels
    Menghang Xia
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Toxicol Appl Pharmacol 252:250-8. 2011
    ..Profiling environmental compound libraries for hERG channel inhibition provides information useful in prioritizing these compounds for cardiotoxicity assessment in vivo...
  35. pmc Profiling environmental chemicals for activity in the antioxidant response element signaling pathway using a high throughput screening approach
    Sunita J Shukla
    NIH Chemical Genomics Center, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, USA
    Environ Health Perspect 120:1150-6. 2012
    ..Thus, assays that detect the up-regulation of this pathway could be useful for identifying chemicals that induce oxidative stress...
  36. pmc A quantitative high-throughput screen for modulators of IL-6 signaling: a model for interrogating biological networks using chemical libraries
    Ronald L Johnson
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biosyst 5:1039-50. 2009
    ..Small molecules within these series will make useful tool compounds to investigate IL-6 signaling mediated by JAK-STAT activation...
  37. pmc Inhibition of morphine-induced cAMP overshoot: a cell-based assay model in a high-throughput format
    Menghang Xia
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell Mol Neurobiol 31:901-7. 2011
    ..The qHTS approach we used in this study will be useful in identifying novel inhibitors of morphine induced addiction from a larger scale screening...
  38. ncbi request reprint High-throughput screening assays for the identification of chemical probes
    James Inglese
    US National Institutes of Health Chemical Genomics Center, National Institutes of Health, 9800 Medical Center Drive, Bethesda, Maryland 20892 3370, USA
    Nat Chem Biol 3:466-79. 2007
    ..We conclude with special considerations for configuring sensitive, robust, informative and economically feasible HTS assays...
  39. pmc A high-throughput approach for identification of novel general anesthetics
    Wendy A Lea
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
    PLoS ONE 4:e7150. 2009
    ..These hits were validated using isothermal titration calorimetry. The success of this initial screen and computational triage provides feasibility to undergo a large scale campaign to discover novel general anesthetics...
  40. pmc Weighted feature significance: a simple, interpretable model of compound toxicity based on the statistical enrichment of structural features
    Ruili Huang
    Department of Health and Human Services, NIH Chemical Genomics Center, National Institutes of Health, Bethesda, Maryland 20892 3370, USA
    Toxicol Sci 112:385-93. 2009
    ..The new algorithm has the important advantages of simplicity, power, interpretability, and ease of implementation...
  41. pmc Comprehensive characterization of cytochrome P450 isozyme selectivity across chemical libraries
    Henrike Veith
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, Maryland, USA
    Nat Biotechnol 27:1050-5. 2009
    ..We also identified chemical substructures that differentiated between the five isozymes. The pharmacological compendium described here should further the understanding of CYP isozymes...
  42. pmc The NCGC pharmaceutical collection: a comprehensive resource of clinically approved drugs enabling repurposing and chemical genomics
    Ruili Huang
    National Institutes of Health Chemical Genomics Center, NIH, Bethesda, MD 20892, USA
    Sci Transl Med 3:80ps16. 2011
    ..We report here the creation of a definitive, complete, and nonredundant list of all approved molecular entities as a freely available electronic resource and a physical collection of small molecules amenable to high-throughput screening...
  43. pmc Quantitative high-throughput screening using a live-cell cAMP assay identifies small-molecule agonists of the TSH receptor
    Steve Titus
    National Institutes of Health Chemical Genomics Center, National Human Genome Research Institute, NIH, Bethesda, MD 20892 3370, USA
    J Biomol Screen 13:120-7. 2008
    ..Forty-nine compounds in several structural classes have been confirmed as the small-molecule TSHR agonists that will serve as a starting point for chemical optimization and studies of thyroid physiology in health and disease...
  44. pmc A novel brain penetrant NPS receptor antagonist, NCGC00185684, blocks alcohol-induced ERK-phosphorylation in the central amygdala and decreases operant alcohol self-administration in rats
    Annika Thorsell
    Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892, USA
    J Neurosci 33:10132-42. 2013
    ..Together, these data provide an initial validation of the NPSR as a therapeutic target in alcoholism...
  45. pmc Identification of clinically used drugs that activate pregnane X receptors
    Sunita J Shukla
    National Institutes of Health Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
    Drug Metab Dispos 39:151-9. 2011
    ....
  46. pmc Identification of chemical compounds that induce HIF-1alpha activity
    Menghang Xia
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, Maryland 20892, USA
    Toxicol Sci 112:153-63. 2009
    ..Identification of environmental compounds having HIF-1alpha activation activity in cell-based assays may be useful for prioritizing chemicals for further testing as hypoxia-response inducers in vivo...
  47. pmc Identification of known drugs that act as inhibitors of NF-kappaB signaling and their mechanism of action
    Susanne C Miller
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Biochem Pharmacol 79:1272-80. 2010
    ..Comprehensive profiling of approved drugs provides insight into their molecular mechanisms, thus providing a basis for drug repurposing...
  48. pmc A cell-based PDE4 assay in 1536-well plate format for high-throughput screening
    Steven A Titus
    NIH Chemical Genomics Center, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892 3370, USA
    J Biomol Screen 13:609-18. 2008
    ....
  49. pmc Synthesis and evaluation of quinazolin-4-ones as hypoxia-inducible factor-1α inhibitors
    Wenwei Huang
    NIH Chemical Genomics Center, National Human Genome Research Institute, NIH, 9800 Medical Center Dr, Rockville, MD 20850, USA
    Bioorg Med Chem Lett 21:5239-43. 2011
    ..In this Letter, we describe an efficient one-pot sequential reaction for the synthesis of quinazolin-4-one 1 analogues. The structure-activity relationship (SAR) study led to the 5-fold more potent analogue, 16...
  50. pmc Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum
    Jing Yuan
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA
    Nat Chem Biol 5:765-71. 2009
    ..This study identifies new leads for antimalarial drugs and demonstrates the utility of a high-throughput chemical genomic strategy for studying malaria traits...
  51. pmc Compound cytotoxicity profiling using quantitative high-throughput screening
    Menghang Xia
    NIH Chemical Genomics Center, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892 3370, USA
    Environ Health Perspect 116:284-91. 2008
    ..Such methods can be relatively expensive, low-throughput, and associated with pain suffered by the treated animals. In addition, differences in species biology may confound extrapolation to human health effects...
  52. pmc A bioluminescent cytotoxicity assay for assessment of membrane integrity using a proteolytic biomarker
    Ming Hsuang Cho
    NIH Chemical Genomics Center, National Institutes of Health, 9800 Medical Center Drive, MSC 3370, Bethesda, MD 20892 3370, USA
    Toxicol In Vitro 22:1099-106. 2008
    ..This cytotoxicity assay, combined with the qHTS platform, allowed us to quickly and efficiently evaluate compound toxicities related to cell membrane integrity...
  53. pmc The Tox21 robotic platform for the assessment of environmental chemicals - from vision to reality
    Matias S Attene-Ramos
    NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA
    Drug Discov Today 18:716-23. 2013
    ..In this article, we describe the Tox21 screening process, compound library preparation, data processing, and robotic system validation. ..
  54. pmc High-throughput genotoxicity assay identifies antioxidants as inducers of DNA damage response and cell death
    Jennifer T Fox
    Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 109:5423-8. 2012
    ..Furthermore, resveratrol and genistein killed multidrug-resistant cancer cells. We therefore propose that resveratrol, genistein, and baicalein are attractive candidates for improved chemotherapeutic agents...
  55. pmc High-throughput Giardia lamblia viability assay using bioluminescent ATP content measurements
    Catherine Z Chen
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892 3370, USA
    Antimicrob Agents Chemother 55:667-75. 2011
    ..The most potent novel compound was fumagillin, which showed 50% inhibitory concentrations of 10 nM against the WB isolate and 2 nM against the GS isolate...
  56. pmc Discovery, synthesis, and biological evaluation of novel SMN protein modulators
    Jingbo Xiao
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Rockville, Maryland 20850, USA
    J Med Chem 54:6215-33. 2011
    ..We anticipate that a lead candidate chosen from this series may serve as a useful probe for exploring the therapeutic benefits of SMN protein up-regulation in SMA animal models and a starting point for clinical development...
  57. pmc A quantitative high-throughput screen identifies novel inhibitors of the interaction of thyroid receptor beta with a peptide of steroid receptor coactivator 2
    Ronald L Johnson
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
    J Biomol Screen 16:618-27. 2011
    ..Selected compounds were tested as independent samples, and a methylsulfonylnitrobenzoate series inhibited the TRβ-SRC2 interaction with 5 µM IC(50). This series represents a new class of thyroid hormone receptor-coactivator modulators...
  58. pmc A 1,536-well-based kinetic HTS assay for inhibitors of Schistosoma mansoni thioredoxin glutathione reductase
    Wendy A Lea
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Assay Drug Dev Technol 6:551-5. 2008
    ..This assay is further applicable to the testing of other redox enzymes that utilize DTNB as a model substrate...
  59. pmc A new resorufin-based alpha-glucosidase assay for high-throughput screening
    Omid Motabar
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Anal Biochem 390:79-84. 2009
    ..Therefore, this new fluorogenic substrate is a useful tool for the alpha-glucosidase enzyme assay and will facilitate compound screening for the development of new therapies for Pompe disease...
  60. pmc δ-Tocopherol reduces lipid accumulation in Niemann-Pick type C1 and Wolman cholesterol storage disorders
    Miao Xu
    National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 287:39349-60. 2012
    ..Our data suggest that regulated exocytosis may represent a potential therapeutic target for reduction of lysosomal storage in this class of diseases...
  61. pmc Two high-throughput screening assays for aberrant RNA-protein interactions in myotonic dystrophy type 1
    Catherine Z Chen
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Anal Bioanal Chem 402:1889-98. 2012
    ..These assays are homogenous and successfully miniaturized to 1,536-well plate format. Both assays were validated and show robust signal-to-basal ratios and Z' factors...
  62. pmc Phosphodiesterase 4 inhibitors enhance sexual pleasure-seeking activity in rodents
    Peixiong Yuan
    Biomarker Laboratory, National Institute of Mental Health, Mood and Anxiety Disorders Program, National Institutes of Health, Bethesda, MD 20892, USA
    Pharmacol Biochem Behav 98:349-55. 2011
    ..The results suggest that PDE4 may be a plausible contributor to the sexual pleasure-seeking deficits seen in depressed patients; inhibiting PDE4 may restore these deficits...
  63. pmc Chemical genomics profiling of environmental chemical modulation of human nuclear receptors
    Ruili Huang
    National Institutes of Health Chemical Genomics Center, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892 3370, USA
    Environ Health Perspect 119:1142-8. 2011
    ....
  64. pmc N4-phenyl modifications of N2-(2-hydroxyl)ethyl-6-(pyrrolidin-1-yl)-1,3,5-triazine-2,4-diamines enhance glucocerebrosidase inhibition by small molecules with potential as chemical chaperones for Gaucher disease
    Wenwei Huang
    NIH Chemical Genomics Center, National Human Genome Research Institute, NIH, 9800 Medical Center Drive, MSC 3370, Bethesda, MD 20892 3370, USA
    Bioorg Med Chem Lett 17:5783-9. 2007
    ..Synthesis, structure activity relationships and the selectivity of chosen analogues against related sugar hydrolases enzymes are described...
  65. ncbi request reprint Fluorescent protein-based cellular assays analyzed by laser-scanning microplate cytometry in 1536-well plate format
    Douglas S Auld
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, MD 20892, USA
    Methods Enzymol 414:566-89. 2006
    ..This chapter illustrates the application of microplate laser cytometry to these assays in a manner that is suitable for screening large compound collections in high throughput...
  66. ncbi request reprint Evaluation of micro-parallel liquid chromatography as a method for HTS-coupled actives verification
    Anton Simeonov
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Assay Drug Dev Technol 5:815-24. 2007
    ..We discuss the benefits of microPLC and its limitations from the standpoint of ease of use and integration into a seamless postscreen workflow...
  67. pmc A dual-fluorescence high-throughput cell line system for probing multidrug resistance
    Kyle R Brimacombe
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Assay Drug Dev Technol 7:233-49. 2009
    ....
  68. pmc A new homogeneous high-throughput screening assay for profiling compound activity on the human ether-a-go-go-related gene channel
    Steven A Titus
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Anal Biochem 394:30-8. 2009
    ..Our findings indicate that this thallium flux assay can be used as an alternative method to profile large-volume compound libraries for compound activity on the hERG channel...
  69. pmc Dual-fluorophore quantitative high-throughput screen for inhibitors of BRCT-phosphoprotein interaction
    Anton Simeonov
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Anal Biochem 375:60-70. 2008
    ..Faced with a traditionally difficult protein-protein interaction assay, by performing two-fluorophore qHTS, we were able to confidently select a number of actives for further studies...
  70. pmc Comparison on Functional Assays for Gq-Coupled GPCRs by Measuring Inositol Monophospate-1 and Intracellular Calcium in 1536-Well Plate Format
    Ke Liu
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Curr Chem Genomics 1:70-8. 2008
    ..This IP-One assay offers an alternative method for high throughput screening of Gq-coupled GPCRs without using costly kinetic plate readers...
  71. pmc A real-time fluorescence method for enzymatic characterization of specialized human DNA polymerases
    Dorjbal Dorjsuren
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Nucleic Acids Res 37:e128. 2009
    ..The fluorogenic method presented here should facilitate mechanistic and inhibitor investigations of these polymerases and is also applicable to the study of highly processive replicative polymerases...
  72. pmc Identification of pregnane X receptor ligands using time-resolved fluorescence resonance energy transfer and quantitative high-throughput screening
    Sunita J Shukla
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, Maryland, USA
    Assay Drug Dev Technol 7:143-69. 2009
    ..The CRC information was also used to define chemotypes associated with PXR ligands. This study demonstrates the feasibility of profiling thousands of compounds against PXR using the TR-FRET assay in a high-throughput format...
  73. pmc A high throughput fluorescence polarization assay for inhibitors of the GoLoco motif/G-alpha interaction
    Adam J Kimple
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Comb Chem High Throughput Screen 11:396-409. 2008
    ..84 and 0.66 for the green- and red-label assays, respectively...
  74. pmc Quantitative high-throughput screening: a titration-based approach that efficiently identifies biological activities in large chemical libraries
    James Inglese
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Proc Natl Acad Sci U S A 103:11473-8. 2006
    ..qHTS produces rich data sets that can be immediately mined for reliable biological activities, thereby providing a platform for chemical genomics and accelerating the identification of leads for drug discovery...
  75. pmc Three classes of glucocerebrosidase inhibitors identified by quantitative high-throughput screening are chaperone leads for Gaucher disease
    Wei Zheng
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, 9800 Medical Center Drive, MSC 3370, Bethesda, MD 20892 3370, USA
    Proc Natl Acad Sci U S A 104:13192-7. 2007
    ..These small molecules have potential as leads for chaperone therapy for Gaucher disease, and this paradigm promises to accelerate the development of leads for other rare genetic disorders...
  76. ncbi request reprint A cell-based assay for IkappaBalpha stabilization using a two-color dual luciferase-based sensor
    R Eric Davis
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892 3370, USA
    Assay Drug Dev Technol 5:85-103. 2007
    ..Known and unexpected inhibitors of NFkappaB signaling were identified from the bioactive collection. We describe here the development and performance of this assay, and discuss the merits of its specific features...
  77. pmc Tetracycline-inducible gene expression in conditionally immortalized mouse podocytes
    Hiroshi Kajiyama
    Kidney Disease Section, Kidney Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD 20892 1268, USA
    Am J Nephrol 29:153-63. 2009
    ..Conditionally immortalized podocytes are valuable research tools but are difficult to efficiently transfect and do not provide graded transgene expression...
  78. pmc Identification of a potent new chemotype for the selective inhibition of PDE4
    Amanda P Skoumbourdis
    NIH Chemical Genomics Center, National Human Genome Research Institute, NIH, 9800 Medical Center Drive, MSC 3370, Bethesda, MD 20892 3370, USA
    Bioorg Med Chem Lett 18:1297-303. 2008
    ..Synthesis, structure-activity relationships, and the selectivity of a highly potent analogue against related phosphodiesterase isoforms are presented...
  79. ncbi request reprint Measure, mine, model, and manipulate: the future for HTS and chemoinformatics?
    Christian N Parker
    Drug Discov Today 11:863-5. 2006
  80. ncbi request reprint Cloning and characterization of Disc1, the mouse ortholog of DISC1 (Disrupted-in-Schizophrenia 1)
    Lei Ma
    Department of Neuroscience, West Point, Pennsylvania 19486, USA
    Genomics 80:662-72. 2002
    ..Identification of Disc1 will facilitate the study of DISC1's function and creation of mouse models of DISC1 disruption...
  81. ncbi request reprint DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation
    Jill A Morris
    Department of Neuroscience, Merck Research Laboratories, West Point, PA 19486, USA
    Hum Mol Genet 12:1591-608. 2003
    ....
  82. ncbi request reprint Identification, localization and receptor characterization of novel mammalian substance P-like peptides
    Marc M Kurtz
    Department of Immunology Rheumatology, Merck Research Laboratories, Rahway, NJ 07065, USA
    Gene 296:205-12. 2002
    ..The results indicate that PPT-C encodes another high affinity ligand of the NK1 receptor which may play an important role in mediating some of the physiological roles previously assigned to the NK1 receptor...
  83. ncbi request reprint Melanin-concentrating hormone receptor subtypes 1 and 2: species-specific gene expression
    Carina P Tan
    Department of Obesity and Metabolic Research, Merck Research Laboratories, Rahway, NJ 07065, USA
    Genomics 79:785-92. 2002
    ....
  84. ncbi request reprint A high-throughput screen for aggregation-based inhibition in a large compound library
    Brian Y Feng
    Department of Pharmaceutical Chemistry and Graduate Group in Chemistry and Chemical Biology, 1700 4th Street, University of California San Francisco, San Francisco, California 94158 2330, USA
    J Med Chem 50:2385-90. 2007
    ..Third, aggregate-based inhibition is correlated with steep dose-response curves, although not absolutely. The results of this screen are being released publicly via the PubChem database...
  85. pmc Identification of oxadiazoles as new drug leads for the control of schistosomiasis
    Ahmed A Sayed
    Department of Biological Sciences, Illinois State University, Normal, Illinois 61790, USA
    Nat Med 14:407-12. 2008
    ..The compound was active against the three major schistosome species infecting humans. These protective effects exceed benchmark activity criteria set by the World Health Organization for lead compound development for schistosomiasis...
  86. 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...
  87. pmc Identification of N-(quinolin-8-yl)benzenesulfonamides as agents capable of down-regulating NFkappaB activity within two separate high-throughput screens of NFkappaB activation
    Yuli Xie
    Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, Columbia University, 630 West 168th Street, New York, NY 10032, USA
    Bioorg Med Chem Lett 18:329-35. 2008
    ..The series exhibited potencies in the cell-based assays at as low as 0.6 microM, and several indications suggest that the targeted activity lies within a common region of the NFkappaB pathway...
  88. ncbi request reprint Molecular characterization of the murine SIGNR1 gene encoding a C-type lectin homologous to human DC-SIGN and DC-SIGNR
    Stephen A Parent
    Department of Immunology and Rheumatology, Merck Research Laboratories, PO Box 2000, RY 80Y 225, Rahway, NJ 07065, USA
    Gene 293:33-46. 2002
    ..In situ hybridization and immunocytochemistry experiments demonstrate that, like human DC-SIGN, the murine messenger RNAs are expressed in subsets of dendritic cells in the spleen and skin...