Anton Simeonov

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc High-throughput fluorescence imaging approaches for drug discovery using in vitro and in vivo three-dimensional models
    Natalia J Martinez
    a National Institutes of Health, National Center for Advancing Translational Sciences, Rockville, MD 20850, USA
    Expert Opin Drug Discov 10:1347-61. 2015
  2. pmc Current approaches for the discovery of drugs that deter substance and drug abuse
    Adam Yasgar
    National Institutes of Health, NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, Bethesda, MD, USA 1 301 217 5721 1 301 217 5736
    Expert Opin Drug Discov 9:1319-31. 2014
  3. pmc Methods for Activity Analysis of the Proteins that Regulate Histone Methylation
    Amy M Quinn
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Curr Chem Genomics 5:95-105. 2011
  4. pmc Quantitative high-throughput screening identifies 8-hydroxyquinolines as cell-active histone demethylase inhibitors
    Oliver N F King
    Structural Genomics Consortium, University of Oxford, Headington, United Kingdom
    PLoS ONE 5:e15535. 2010
  5. pmc Recent developments in the use of differential scanning fluorometry in protein and small molecule discovery and characterization
    Anton Simeonov
    National Institutes of Health, National Center for Advancing Translational Sciences, Division of Discovery Innovation, 9800 Medical Center Drive, Bethesda, MD 20892 3370, USA
    Expert Opin Drug Discov 8:1071-82. 2013
  6. 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
  7. 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
  8. 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
  9. 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
  10. pmc Diverse small molecule inhibitors of human apurinic/apyrimidinic endonuclease APE1 identified from a screen of a large public collection
    Dorjbal Dorjsuren
    NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 7:e47974. 2012

Collaborators

Detail Information

Publications78

  1. pmc High-throughput fluorescence imaging approaches for drug discovery using in vitro and in vivo three-dimensional models
    Natalia J Martinez
    a National Institutes of Health, National Center for Advancing Translational Sciences, Rockville, MD 20850, USA
    Expert Opin Drug Discov 10:1347-61. 2015
    ..Combined, the use of imaging-based 3D models in the early stages of drug development has the potential to generate biologically relevant data that will increase the likelihood of success for drug candidates in human studies...
  2. pmc Current approaches for the discovery of drugs that deter substance and drug abuse
    Adam Yasgar
    National Institutes of Health, NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, Bethesda, MD, USA 1 301 217 5721 1 301 217 5736
    Expert Opin Drug Discov 9:1319-31. 2014
    ....
  3. pmc Methods for Activity Analysis of the Proteins that Regulate Histone Methylation
    Amy M Quinn
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Curr Chem Genomics 5:95-105. 2011
    ..Progress in the development of high-throughput, sensitive, and robust assays will enable discovery of small molecules for epigenetic therapy...
  4. pmc Quantitative high-throughput screening identifies 8-hydroxyquinolines as cell-active histone demethylase inhibitors
    Oliver N F King
    Structural Genomics Consortium, University of Oxford, Headington, United Kingdom
    PLoS ONE 5:e15535. 2010
    ..There are few reports on the identification of templates that are amenable to development as potent inhibitors in vivo and large diverse collections have yet to be exploited for the discovery of demethylase inhibitors...
  5. pmc Recent developments in the use of differential scanning fluorometry in protein and small molecule discovery and characterization
    Anton Simeonov
    National Institutes of Health, National Center for Advancing Translational Sciences, Division of Discovery Innovation, 9800 Medical Center Drive, Bethesda, MD 20892 3370, USA
    Expert Opin Drug Discov 8:1071-82. 2013
    ..This technique monitors protein through the use of environmentally sensitive fluorescent dye, in a temperature-ramp regime by observing the gradual exposure to the solvent of otherwise buried hydrophobic faces of protein domains...
  6. 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...
  7. 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...
  8. 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...
  9. 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...
  10. pmc Diverse small molecule inhibitors of human apurinic/apyrimidinic endonuclease APE1 identified from a screen of a large public collection
    Dorjbal Dorjsuren
    NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 7:e47974. 2012
    ..To our knowledge, this represents the largest-scale HTS to identify inhibitors of APE1, and provides a key first step in the development of novel agents targeting BER for cancer treatment...
  11. 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...
  12. pmc 4-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide (ML267), a potent inhibitor of bacterial phosphopantetheinyl transferase that attenuates secondary metabolism and thwarts bacterial growth
    Timothy L Foley
    National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States
    J Med Chem 57:1063-78. 2014
    ..Additionally, we highlight the in vitro absorption, distribution, metabolism, and excretion and in vivo pharmacokinetic profiles of compound 55 to further demonstrate the potential utility of this small-molecule inhibitor. ..
  13. 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...
  14. 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
    ....
  15. pmc Differential scanning fluorometry signatures as indicators of enzyme inhibitor mode of action: case study of glutathione S-transferase
    Wendy A Lea
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
    PLoS ONE 7:e36219. 2012
    ..The results illustrate the potential of DSF as a tool to differentiate diverse classes of inhibitors based on simple analysis of co-substrate dependency of protein stabilization...
  16. pmc High-affinity inhibitors of human NAD-dependent 15-hydroxyprostaglandin dehydrogenase: mechanisms of inhibition and structure-activity relationships
    Frank H Niesen
    Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
    PLoS ONE 5:e13719. 2010
    ..High-affinity probes for 15-PGDH will, therefore, represent important tools for further studies...
  17. pmc A highly potent and selective caspase 1 inhibitor that utilizes a key 3-cyanopropanoic acid moiety
    Matthew B Boxer
    National Institutes of Health, National Human Genome Research Institute, NIH Chemical Genomics Center, Rockville, Maryland 20850, USA
    ChemMedChem 5:730-8. 2010
    ..Assessment of hydrolytic stability and selected ADME properties highlighted these agents as potentially useful tools for studying caspase 1 down-regulation in various settings, including in vivo analyses...
  18. 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
    ....
  19. 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...
  20. 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
    ....
  21. 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...
  22. 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...
  23. 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...
  24. 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...
  25. 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...
  26. 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...
  27. pmc Discovery of potent and selective inhibitors of human platelet-type 12- lipoxygenase
    Victor Kenyon
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892 3370, United States
    J Med Chem 54:5485-97. 2011
    ..In addition, these compounds demonstrate efficacy in cellular models, which underscores their relevance to disease modification...
  28. pmc Discovery of potent and selective inhibitors of human reticulocyte 15-lipoxygenase-1
    Ganesha Rai
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, 9800 Medical Center Drive, MSC 3370, Bethesda, Maryland 20892, USA
    J Med Chem 53:7392-404. 2010
    ..In addition, kinetic experiments were performed which indicate that this class of inhibitor is tight binding, reversible, and appears not to reduce the active-site ferric ion...
  29. pmc A High-Throughput Screen Identifies 2,9-Diazaspiro[5.5]Undecanes as Inducers of the Endoplasmic Reticulum Stress Response with Cytotoxic Activity in 3D Glioma Cell Models
    Natalia J Martinez
    National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, United States of America
    PLoS ONE 11:e0161486. 2016
    ..This study demonstrates that our screening platform enables the identification and profiling of ERSR inducers with cytotoxic activity and advocates for characterization of these compound in in vivo models. ..
  30. pmc A miniaturized screen for inhibitors of Jumonji histone demethylases
    Masaaki Sakurai
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Mol Biosyst 6:357-64. 2010
    ..The assay developed here will enable the screening of large compound libraries against the Jumonji demethylases in a robust and automated fashion...
  31. 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...
  32. pmc Synthesis and structure-activity relationship studies of 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives as potent and selective inhibitors of 12-lipoxygenase
    Diane K Luci
    National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States
    J Med Chem 57:495-506. 2014
    ..In addition, both compounds inhibit PAR-4 induced aggregation and calcium mobilization in human platelets and reduce 12-HETE in β-cells. ..
  33. pmc Discovery of a novel noniminosugar acid α glucosidase chaperone series
    Jingbo Xiao
    NIH Chemical Genomics Center, NIH Center for Translational Therapeutics, National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, USA
    J Med Chem 55:7546-59. 2012
    ..AMDE and physical properties studies indicate that this series is a promising lead for further pharmacokinetic evaluation and testing in Pompe disease models...
  34. pmc Synthesis, biological evaluation, and structure-activity relationships of a novel class of apurinic/apyrimidinic endonuclease 1 inhibitors
    Ganesha Rai
    NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland 20892 3370, USA
    J Med Chem 55:3101-12. 2012
    ..Moreover, this class of compounds possesses a generally favorable in vitro ADME profile, along with good exposure levels in plasma and brain following intraperitoneal dosing (30 mg/kg body weight) in mice...
  35. pmc Profiling of the Tox21 chemical collection for mitochondrial function to identify compounds that acutely decrease mitochondrial membrane potential
    Matias S Attene-Ramos
    National Center for Advancing Translational Sciences, National Institutes of Health NIH, Department of Health and Human Services DHHS, Bethesda, Maryland, USA
    Environ Health Perspect 123:49-56. 2015
    ....
  36. 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
    ....
  37. 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...
  38. pmc Structure-activity relationship studies and biological characterization of human NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase inhibitors
    Damien Y Duveau
    National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States
    Bioorg Med Chem Lett 24:630-5. 2014
    ..Top compounds from both series displayed potent inhibition (IC50 <50 nM), demonstrate excellent selectivity towards HPGD and potently induce PGE2 production in A549 lung cancer and LNCaP prostate cancer cells...
  39. 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...
  40. pmc A chemiluminescence-based method for identification of histone lysine methyltransferase inhibitors
    Amy M Quinn
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesada, MD 20892 3370, USA
    Mol Biosyst 6:782-8. 2010
    ..The method is particularly well suited for detection of inhibitors acting by the desired histone peptide competitive mechanism and is applicable to testing other HMTs, demonstrated here with the G9a homolog EHMT1, also known as GLP...
  41. 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...
  42. pmc Synthesis and structure-activity relationship studies of N-benzyl-2-phenylpyrimidin-4-amine derivatives as potent USP1/UAF1 deubiquitinase inhibitors with anticancer activity against nonsmall cell lung cancer
    Thomas S Dexheimer
    National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States
    J Med Chem 57:8099-110. 2014
    ..Our results establish the druggability of the USP1/UAF1 deubiquitinase complex and its potential as a molecular target for anticancer therapies. ..
  43. 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...
  44. pmc A homogeneous method for investigation of methylation-dependent protein-protein interactions in epigenetics
    Amy M Quinn
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Nucleic Acids Res 38:e11. 2010
    ..The simplicity of design and the sensitive and robust nature of this assay should make it applicable to a range of epigenetic studies, including the search for novel inhibitors of methylation-dependent interactions...
  45. pmc Complementary non-radioactive assays for investigation of human flap endonuclease 1 activity
    Dorjbal Dorjsuren
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 3370, USA
    Nucleic Acids Res 39:e11. 2011
    ..59 and 0.93 µM, respectively). The availability of these simple complementary assays obviates the need for undesirable radiotracer-based assays and should facilitate efforts to develop novel inhibitors for this key biological target...
  46. pmc Discovery of a novel general anesthetic chemotype using high-throughput screening
    Andrew R McKinstry-Wu
    From the Department of Anesthesiology and Critical Care A R M W, W B, R G E and Department of Pharmacology B P W, University of Pennsylvania, Philadelphia, Pennsylvania National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland G R, W A L, A s, A J, D J M and College of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania D F L
    Anesthesiology 122:325-33. 2015
    ..The development of novel anesthetics has historically been a process of combined serendipity and empiricism, with most recent new anesthetics developed via modification of existing anesthetic structures...
  47. 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...
  48. 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. ..
  49. pmc Exploratory analysis of kinetic solubility measurements of a small molecule library
    Rajarshi Guha
    NIH Chemical Genomics Center, National Human Genome Research Institute, NIH, Bethesda, MD 20892 3370, USA
    Bioorg Med Chem 19:4127-34. 2011
    ..The results of this solubility profile should aid chemists during library design and optimization efforts and represent a useful training set for computational solubility prediction...
  50. pmc A Platform to Enable the Pharmacological Profiling of Small Molecules in Gel-Based Electrophoretic Mobility Shift Assays
    Timothy L Foley
    Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA Primary Pharmacology Group, Pharmacokinetics, Dynamics and Metabolism New Chemical Entities, Pfizer, Groton, CT, USA
    J Biomol Screen . 2016
    ..Throughputs of greater than 1000 samples per day were achieved when this system was paired with a quantitative laser-based imaging system, yielding data of remarkable quality...
  51. pmc Suppression of the FOXM1 transcriptional programme via novel small molecule inhibition
    Michael V Gormally
    1 University Chemical Laboratory, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK 2 Cancer Research UK, Li Ka Shing Centre, Cambridge Institute, Cambridge CB2 0RE, UK 3 National Center for Advancing Translational Sciences, NIH, Rockville, Maryland 20850, USA
    Nat Commun 5:5165. 2014
    ..This small molecule-mediated effect is selective for FOXM1-controlled genes with no effect on genes regulated by homologous forkhead family factors...
  52. doi request reprint Modelling the Tox21 10 K chemical profiles for in vivo toxicity prediction and mechanism characterization
    Ruili Huang
    Division of Pre clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, USA
    Nat Commun 7:10425. 2016
    ..Our results suggest that in vitro activity profiles can be applied as signatures of compound mechanism of toxicity and used in prioritization for more in-depth toxicological testing...
  53. 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...
  54. pmc Biochemical, cellular, and biophysical characterization of a potent inhibitor of mutant isocitrate dehydrogenase IDH1
    Mindy I Davis
    From the NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20892
    J Biol Chem 289:13717-25. 2014
    ..In the presence of racemic ML309, 2-HG levels drop rapidly. This drop was sustained until 48 h, at which point the compound was washed out and 2-HG levels recovered. ..
  55. pmc Structural insight into exosite binding and discovery of novel exosite inhibitors of botulinum neurotoxin serotype A through in silico screening
    Xin Hu
    NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA
    J Comput Aided Mol Des 28:765-78. 2014
    ..The identified exosite inhibitors may provide novel candidates for structure-based development of therapeutics against BoNT/A intoxication. ..
  56. pmc Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase
    Andrew S Rosenthal
    National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States
    Bioorg Med Chem Lett 23:5660-6. 2013
    ..Moreover, these compounds demonstrated cellular activity by inducing sister chromatid exchanges, a hallmark of Bloom syndrome. ..
  57. pmc High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell-like diffuse large B-cell lymphoma cells
    Lesley A Mathews Griner
    Division of Preclinical Innovation, National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Metabolism Branch, Center for Cancer Research, and Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 111:2349-54. 2014
    ....
  58. pmc Disrupting malaria parasite AMA1-RON2 interaction with a small molecule prevents erythrocyte invasion
    Prakash Srinivasan
    Laboratory of Malaria and Vector Research, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20852, USA
    Nat Commun 4:2261. 2013
    ..This study uncovers a strategy that will allow for highly effective combination therapies alongside existing antimalarial drugs. ..
  59. pmc Targeting the JMJD2 histone demethylases to epigenetically control herpesvirus infection and reactivation from latency
    Yu Liang
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Sci Transl Med 5:167ra5. 2013
    ....
  60. pmc Small molecule inhibitors of DNA repair nuclease activities of APE1
    David M Wilson
    Laboratory of Molecular Gerontology, Biomedical Research Center, National Institute on Aging, NIH, IRP, 251 Bayview Boulevard, Baltimore, MD 21224, USA
    Cell Mol Life Sci 67:3621-31. 2010
    ..In this review, we summarize the current state of the efforts to design potent and selective inhibitors against APE1 AP site incision activity...
  61. pmc Diaphorase Coupling Protocols for Red-Shifting Dehydrogenase Assays
    Mindy I Davis
    NCATS Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland
    Assay Drug Dev Technol 14:207-12. 2016
    ..This coupling technique is applicable to dehydrogenases that either produce or consume NAD(P)H, and the examples provided here can act as guidelines for the development of high-throughput screens against this enzyme class. ..
  62. pmc Small Molecule Inhibition of the Ubiquitin-specific Protease USP2 Accelerates cyclin D1 Degradation and Leads to Cell Cycle Arrest in Colorectal Cancer and Mantle Cell Lymphoma Models
    Mindy I Davis
    From the NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20892
    J Biol Chem 291:24628-24640. 2016
    ..These effects by a small molecule inhibitor support a key role for USP2 as a regulator of cell cycle, DNA repair, and tumor cell growth...
  63. pmc Inheritance of rare functional GCKR variants and their contribution to triglyceride levels in families
    Matthew G Rees
    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LE, UK, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA
    Hum Mol Genet 23:5570-8. 2014
    ..Therefore, despite evidence for their collective functional and clinical relevance, our results emphasize the low predictive value of rare GCKR variants in individuals and the complex heritability of lipid traits. ..
  64. pmc High-throughput 1,536-well fluorescence polarization assays for α(1)-acid glycoprotein and human serum albumin binding
    Adam Yasgar
    NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA
    PLoS ONE 7:e45594. 2012
    ..The adaptation of the AGP and HSA FP assays to a 1,536-well format should allow their use in early-stage profiling of large-size compound sets...
  65. pmc A homogeneous, high-throughput assay for phosphatidylinositol 5-phosphate 4-kinase with a novel, rapid substrate preparation
    Mindy I Davis
    National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America
    PLoS ONE 8:e54127. 2013
    ..This homogeneous assay may apply to other lipid kinases and should help in the identification of leads for this class of enzymes by enabling high-throughput screening efforts...
  66. pmc A high-throughput assay for small molecule destabilizers of the KRAS oncoprotein
    Joseph Carver
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America
    PLoS ONE 9:e103836. 2014
    ..This proof-of-principle study demonstrates that it is feasible to use a high-throughput screen to identify compounds that promote the degradation of the Ras oncoprotein as a new approach to target Ras. ..
  67. 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...
  68. pmc Method for Assaying the Lipid Kinase Phosphatidylinositol-5-phosphate 4-kinase α in Quantitative High-Throughput Screening (qHTS) Bioluminescent Format
    Mindy I Davis
    Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA
    Methods Mol Biol 1376:1-9. 2016
    ....
  69. pmc Discovery of NCT-501, a Potent and Selective Theophylline-Based Inhibitor of Aldehyde Dehydrogenase 1A1 (ALDH1A1)
    Shyh Ming Yang
    National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States
    J Med Chem 58:5967-78. 2015
    ..Moreover, the pharmacokinetic evaluation of selected analog 64 (NCT-501) is also highlighted. ..
  70. pmc Identification and characterization of inhibitors of human apurinic/apyrimidinic endonuclease APE1
    Anton Simeonov
    NIH Chemical Genomics Center, National Human Genome Research Institute, NIH, Bethesda, MD, USA
    PLoS ONE 4:e5740. 2009
    ..The studies herein report on the identification of novel, small molecule APE1-targeted bioactive inhibitor probes, which represent initial chemotypes towards the development of potential pharmaceuticals...
  71. pmc A panel of diverse assays to interrogate the interaction between glucokinase and glucokinase regulatory protein, two vital proteins in human disease
    Matthew G Rees
    National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, United Kingdom
    PLoS ONE 9:e89335. 2014
    ..The assay panel developed here should help direct future investigation of the GCK-GKRP interaction in these or other physiologically relevant human systems. ..
  72. pmc A small molecule inhibitor of the BLM helicase modulates chromosome stability in human cells
    Giang Huong Nguyen
    Department of Medical Oncology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK
    Chem Biol 20:55-62. 2013
    ..These data indicate that ML216 shows strong selectivity for BLM in cultured cells. We discuss the potential utility of such a BLM-targeting compound as an anticancer agent...
  73. pmc Targeting iron assimilation to develop new antibacterials
    Timothy L Foley
    National Institutes of Health, National Center for Advancing Translational Sciences, Division of Preclinical Innovation, 9800 Medical Center Drive, Bethesda, MD 20892 3370, USA
    Expert Opin Drug Discov 7:831-47. 2012
    ..An ever evolving pipeline of next-generation therapeutics is required for modern medicine to remain one step ahead of pathogens...
  74. pmc Fluorescence polarization assays in small molecule screening
    Wendy A Lea
    National Human Genome Research Institute, National Institutes of Health, NIH Chemical Genomics Center, Bethesda, MD 20892 3370, USA
    Expert Opin Drug Discov 6:17-32. 2011
    ..Recent developments in the field have been symbolized by the facile adoption of FP in high-throughput screening and small molecule drug discovery of an increasing range of target classes...
  75. 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...
  76. 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...
  77. 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...
  78. ncbi request reprint Enzyme assays by fluorescence polarization in the presence of polyarginine: study of kinase, phosphatase, and protease reactions
    Anton Simeonov
    Caliper Technologies Corp, 605 Fairchild Drive, Mountain View, CA 94043, USA
    Anal Biochem 304:193-9. 2002
    ....