James Inglese

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. 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
  2. ncbi request reprint Biology-driven library design for probe discovery
    James Inglese
    NIH Center for Translational Therapeutics, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Chem Biol 18:1204-5. 2011
  3. 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
  4. ncbi request reprint Reporting data from high-throughput screening of small-molecule libraries
    James Inglese
    US National Institutes of Health Chemical Genomics Center, National Human Genome Institute, National Institutes of Health, 9800 Medical Center Drive, Bethesda, Maryland 20892 3370, USA
    Nat Chem Biol 3:438-41. 2007
  5. 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
  6. 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
  7. 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
  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 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
  10. 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

Collaborators

Detail Information

Publications77

  1. 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...
  2. ncbi request reprint Biology-driven library design for probe discovery
    James Inglese
    NIH Center for Translational Therapeutics, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Chem Biol 18:1204-5. 2011
    ..Biology-driven construction methods (Wallace et al., 2011) are rapidly emerging to bring chemical libraries back on a viable path...
  3. 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...
  4. ncbi request reprint Reporting data from high-throughput screening of small-molecule libraries
    James Inglese
    US National Institutes of Health Chemical Genomics Center, National Human Genome Institute, National Institutes of Health, 9800 Medical Center Drive, Bethesda, Maryland 20892 3370, USA
    Nat Chem Biol 3:438-41. 2007
    ..Here, we propose concise guidelines for reporting small-molecule HTS data...
  5. 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...
  6. 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...
  7. 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
    ....
  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 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...
  10. 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...
  11. 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...
  12. 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...
  13. 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...
  14. 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...
  15. 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...
  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 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...
  18. 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...
  19. 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
    ....
  20. 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...
  21. 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...
  22. 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...
  23. pmc Firefly luciferase in chemical biology: a compendium of inhibitors, mechanistic evaluation of chemotypes, and suggested use as a reporter
    Natasha Thorne
    National Center for Advancing Translational Sciences, Bethesda, MD 20892 3370, USA
    Chem Biol 19:1060-72. 2012
    ..As in some cell-based FLuc reporter assays, compounds acting as FLuc inhibitors yield paradoxical luminescence increases, thus data on compounds acquired from FLuc-dependent assays require careful analysis as described here...
  24. 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
    ....
  25. pmc A strategy to discover inhibitors of Bacillus subtilis surfactin-type phosphopantetheinyl transferase
    Adam Yasgar
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Mol Biosyst 6:365-75. 2010
    ..The present assay enables the screening of large compound libraries against Sfp-PPTase in a robust and automated fashion and is applicable to designing assays for related transferase enzymes...
  26. 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...
  27. 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...
  28. 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...
  29. 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...
  30. pmc Mechanism of PTC124 activity in cell-based luciferase assays of nonsense codon suppression
    Douglas S Auld
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Proc Natl Acad Sci U S A 106:3585-90. 2009
    ..Our results demonstrate the value of understanding potential interactions between reporter enzymes and chemical compounds and emphasize the importance of implementing the appropriate control assays before interpreting HTS results...
  31. pmc Molecular basis for the high-affinity binding and stabilization of firefly luciferase by PTC124
    Douglas S Auld
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Proc Natl Acad Sci U S A 107:4878-83. 2010
    ..To our knowledge, this is an unusual example in which the "off-target" effect of a small molecule is mediated by an MAI mechanism...
  32. 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...
  33. pmc A high-throughput 1,536-well luminescence assay for glutathione S-transferase activity
    Adam Yasgar
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892 3370, USA
    Assay Drug Dev Technol 8:200-11. 2010
    ....
  34. 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...
  35. 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...
  36. 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...
  37. 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...
  38. 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...
  39. 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...
  40. 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...
  41. 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...
  42. 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
    ....
  43. 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...
  44. 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...
  45. 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...
  46. 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
    ....
  47. 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...
  48. pmc A specific mechanism for nonspecific activation in reporter-gene assays
    Douglas S Auld
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, Maryland 20892 3370, USA
    ACS Chem Biol 3:463-70. 2008
    ....
  49. 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...
  50. pmc Comparison of bioluminescent kinase assays using substrate depletion and product formation
    Cordelle Tanega
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, Maryland, USA
    Assay Drug Dev Technol 7:606-14. 2009
    ..We conclude that the bioluminescence ADP detection assay system is a viable generic alternative to the widely used ATP-depletion assay for ATPases and discuss the advantages and disadvantages of both approaches...
  51. pmc Identification of phosphotyrosine mimetic inhibitors of human tyrosyl-DNA phosphodiesterase I by a novel AlphaScreen high-throughput assay
    Christophe Marchand
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, 9800 Medical Center Drive, Rockville, MD 20850, USA
    Mol Cancer Ther 8:240-8. 2009
    ..We also report a novel biochemical assay using the SCAN1 Tdp1 mutant to study the mechanism of action of methyl-3,4-dephostatin...
  52. pmc Illuminating insights into firefly luciferase and other bioluminescent reporters used in chemical biology
    Natasha Thorne
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Chem Biol 17:646-57. 2010
    ..The potential influence these findings can have on drug discovery efforts is provided here...
  53. 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...
  54. pmc Apparent activity in high-throughput screening: origins of compound-dependent assay interference
    Natasha Thorne
    NIH Chemical Genomics Center, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Curr Opin Chem Biol 14:315-24. 2010
    ....
  55. 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...
  56. 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...
  57. 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...
  58. 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...
  59. pmc Quantitative high-throughput screening identifies inhibitors of anthrax-induced cell death
    Ping Jun Zhu
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States
    Bioorg Med Chem 17:5139-45. 2009
    ....
  60. 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...
  61. 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...
  62. pmc Innovation in academic chemical screening: filling the gaps in chemical biology
    Samuel A Hasson
    National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA
    Curr Opin Chem Biol 17:329-38. 2013
    ..Importantly, we recognize examples of successful chemical probe development that have punctuated the changing technology landscape...
  63. pmc Identification of drug modulators targeting gene-dosage disease CMT1A
    Sung Wook Jang
    National Center of Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland 20892, United States
    ACS Chem Biol 7:1205-13. 2012
    ..Overall, the findings of this study provide a strategic approach to assay development for gene-dosage diseases such as CMT1A...
  64. 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...
  65. ncbi request reprint Miniaturization of whole live cell-based GPCR assays using microdispensing and detection systems
    Oleg Kornienko
    Merck Research Laboratories, Department of Automated Biotechnology, North Wales, PA 19454, USA
    J Biomol Screen 9:186-95. 2004
    ..These assays were employed in high-throughput screening campaigns, allowing the testing of more than 150,000 compounds in 8 h. The instrumentation used and practical aspects of the assay development are discussed...
  66. ncbi request reprint Identification of metabotropic glutamate receptor antagonists using an automated high-throughput screening system
    Peter Hodder
    Department of Automated Biotechnology, Merck Research Laboratories, North Wales, Pennsylvania 19454, USA
    Anal Biochem 313:246-54. 2003
    ..Primary high-throughput screening hits were subjected to a combination of data analysis and counterscreening assays to identify several compounds with both efficacy and selectivity for the metabotropic glutamate receptor target...
  67. pmc A PDZ domain-based assay for measuring HIV protease activity: assay design considerations
    Aaron C Hamilton
    Department of Automated Biotechnology, North Wales, Pennsylvania 19454, USA
    Protein Sci 12:458-67. 2003
    ..The choices of detection format, for example, TRET or ALPHA, were also investigated and influenced assay design...
  68. ncbi request reprint Expanding the HTS paradigm
    James Inglese
    Drug Discov Today 7:S105-6. 2002
  69. ncbi request reprint A PDZ domain-based detection system for enzymatic assays
    Marc Ferrer
    Department of Automated Biotechnology, Merck Research Laboratories, 503 Louise Lane, North Wales, Pennsylvania 19454, USA
    Anal Biochem 301:207-16. 2002
    ..Reported here are examples of the applicability of this detection strategy to three enzymatic systems, an endoprotease, an exoprotease, and a Ser/Thr phosphatase...
  70. ncbi request reprint Development of an intact cell reporter gene beta-lactamase assay for G protein-coupled receptors for high-throughput screening
    Priya Kunapuli
    Department of Automated Biotechnology, Merck Research Laboratories, 502 Louise Lane, North Wales, PA 19454, USA
    Anal Biochem 314:16-29. 2003
    ..The beta-lactamase assay has been optimized for cell density, time of agonist stimulation, and DMSO sensitivity. This CHO-hBK1-beta-lactamase assay is well suited to automation and miniaturization required for high-throughput screening...
  71. ncbi request reprint A fully automated [35S]GTPgammaS scintillation proximity assay for the high-throughput screening of Gi-linked G protein-coupled receptors
    Marc Ferrer
    Department of Automated Biotechnology, Merck Research Laboratories, North Wales, Pennsylvania, USA
    Assay Drug Dev Technol 1:261-73. 2003
    ..Here we compare [(35)S]GTPgammaS scintillation proximity binding assays for two different G(i)-coupled GPCRs, and describe their implementation with automated high-throughput systems...
  72. ncbi request reprint A 1536-well cAMP assay for Gs- and Gi-coupled receptors using enzyme fragmentation complementation
    Michael Weber
    Department of Automated Biotechnology, Merck Research Laboratories, North Wales, PA 19454, USA
    Assay Drug Dev Technol 2:39-49. 2004
    ....
  73. ncbi request reprint Directed evolution of PDZ variants to generate high-affinity detection reagents
    Marc Ferrer
    Department of Automated Biotechnology, Merck and Co, Inc, 502 503 Louise Lane, North Wales, PA 19454, USA
    Protein Eng Des Sel 18:165-73. 2005
    ..The approach demonstrated here leads the way to highly sensitive reagents for drug discovery that can be isolated more reliably and produced less expensively...
  74. ncbi request reprint A cell-based beta-lactamase reporter gene assay for the identification of inhibitors of hepatitis C virus replication
    Paul Zuck
    Department of Automated Biotechnology, Merck and Co, 502 Louise Lane, North Wales, PA 19454, USA
    Anal Biochem 334:344-55. 2004
    ..HTS was carried out in 384-well microplate format, and the signal-to-background ratio and Z factor for the assay plates during the screen were approximately 13-fold and 0.5, respectively...
  75. 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...
  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. 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...