Paul A Johnston

Summary

Affiliation: University of Pittsburgh
Country: USA

Publications

  1. ncbi request reprint Development and optimization of high-throughput in vitro protein phosphatase screening assays
    Marni Brisson Tierno
    Department of Pharmacology, Pittsburgh Molecular Library Screening Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Nat Protoc 2:1134-44. 2007
  2. pmc Cdc25B dual-specificity phosphatase inhibitors identified in a high-throughput screen of the NIH compound library
    Paul A Johnston
    University of Pittsburgh Drug Discovery Institute, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, Pittsburgh, PA 15260, USA
    Assay Drug Dev Technol 7:250-65. 2009
  3. pmc Redox cycling compounds generate H2O2 in HTS buffers containing strong reducing reagents--real hits or promiscuous artifacts?
    Paul A Johnston
    University of Pittsburgh Drug Discovery Institute, Department of Pharmacology and Chemical Biology, Pittsburgh, PA 15260, USA
    Curr Opin Chem Biol 15:174-82. 2011
  4. pmc Development of a 384-well colorimetric assay to quantify hydrogen peroxide generated by the redox cycling of compounds in the presence of reducing agents
    Paul A Johnston
    Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, Pittsburgh, PA 15260, USA
    Assay Drug Dev Technol 6:505-18. 2008
  5. doi request reprint HTS identifies novel and specific uncompetitive inhibitors of the two-component NS2B-NS3 proteinase of West Nile virus
    Paul A Johnston
    Pittsburgh Molecular Library Screening Center, Department of Pharmacology, University of Pittsburgh Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Assay Drug Dev Technol 5:737-50. 2007
  6. ncbi request reprint Development and implementation of a 384-well homogeneous fluorescence intensity high-throughput screening assay to identify mitogen-activated protein kinase phosphatase-1 dual-specificity protein phosphatase inhibitors
    Paul A Johnston
    Pittsburgh Molecular Libraries Screening Center, Department of Pharmacology, University of Pittsburgh Drug Discovery Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA
    Assay Drug Dev Technol 5:319-32. 2007
  7. pmc Profiling the NIH Small Molecule Repository for compounds that generate H2O2 by redox cycling in reducing environments
    Karina M Soares
    Pittsburgh Molecular Library Screening Center, Drug Discovery Institute, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Assay Drug Dev Technol 8:152-74. 2010
  8. doi request reprint Implementation of a 220,000-compound HCS campaign to identify disruptors of the interaction between p53 and hDM2 and characterization of the confirmed hits
    Drew D Dudgeon
    University of Pittsburgh Drug Discovery Institute, School of Medicine, Pittsburgh, PA, USA
    J Biomol Screen 15:766-82. 2010
  9. pmc Development and validation of a high-content screening assay to identify inhibitors of cytoplasmic dynein-mediated transport of glucocorticoid receptor to the nucleus
    Paul A Johnston
    School of Medicine, University of Pittsburgh Drug Discovery Institute, Pittsburgh, Pennsylvania, USA
    Assay Drug Dev Technol 10:432-56. 2012
  10. ncbi request reprint Synthesis and biological activity of a focused library of mitogen-activated protein kinase phosphatase inhibitors
    David M Arnold
    Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Chem Biol Drug Des 69:23-30. 2007

Collaborators

  • John S Lazo
  • P Wipf
  • Donna M Huryn
  • Joanne I Yeh
  • Naveena Yanamala
  • Elizabeth R Sharlow
  • Nicholas D P Cosford
  • Jeffrey W Smith
  • Kay M Brummond
  • Kenneth A Giuliano
  • Hikmat N Daghestani
  • Tong Ying Shun
  • Drew D Dudgeon
  • Rhonda Gates Williams
  • Oscar J Trask
  • Debra Nickischer
  • Carmen Laethem
  • Sunita N Shinde
  • Ramani Kandasamy
  • Lori A Emert-Sedlak
  • Karina M Soares
  • Christopher J Strock
  • Sager J Gosai
  • D Lansing Taylor
  • Sunita Shinde
  • Shahar Keinan
  • John J Skoko
  • Marni Brisson Tierno
  • Caleb Foster
  • David M Arnold
  • John W Carpenter
  • Purushottam Narute
  • Thomas E Smithgall
  • Jerrod A Poe
  • John Jeff Alvarado
  • Haibin Shi
  • Sherry T Shu
  • David H Perlmutter
  • Kevin J Kovatch
  • Gary A Silverman
  • Joon Hyeok Kwak
  • Dale E King
  • Yun Hua
  • Olivia S Long
  • Cliff J Luke
  • Stephen C Pak
  • Harold K Takyi
  • Nicole Blackmon
  • Weitao Yang
  • William D Paquette
  • David N Beratan
  • Audrey Baker
  • Don McClure
  • David L G Nelson
  • Melvyn Baez
  • Thomas K Eckols
  • Frederick R Hubbard

Detail Information

Publications25

  1. ncbi request reprint Development and optimization of high-throughput in vitro protein phosphatase screening assays
    Marni Brisson Tierno
    Department of Pharmacology, Pittsburgh Molecular Library Screening Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Nat Protoc 2:1134-44. 2007
    ....
  2. pmc Cdc25B dual-specificity phosphatase inhibitors identified in a high-throughput screen of the NIH compound library
    Paul A Johnston
    University of Pittsburgh Drug Discovery Institute, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, Pittsburgh, PA 15260, USA
    Assay Drug Dev Technol 7:250-65. 2009
    ..The availability of non-redox active Cdc25B inhibitors should provide valuable tools to explore the inhibition of the Cdc25 phosphatases as potential mono- or combination therapies for cancer...
  3. pmc Redox cycling compounds generate H2O2 in HTS buffers containing strong reducing reagents--real hits or promiscuous artifacts?
    Paul A Johnston
    University of Pittsburgh Drug Discovery Institute, Department of Pharmacology and Chemical Biology, Pittsburgh, PA 15260, USA
    Curr Opin Chem Biol 15:174-82. 2011
    ..In an attempt to mitigate the serious impact of RCCs on probe and lead generation, two groups have independently developed assays to indentify RCCs...
  4. pmc Development of a 384-well colorimetric assay to quantify hydrogen peroxide generated by the redox cycling of compounds in the presence of reducing agents
    Paul A Johnston
    Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, Pittsburgh, PA 15260, USA
    Assay Drug Dev Technol 6:505-18. 2008
    ....
  5. doi request reprint HTS identifies novel and specific uncompetitive inhibitors of the two-component NS2B-NS3 proteinase of West Nile virus
    Paul A Johnston
    Pittsburgh Molecular Library Screening Center, Department of Pharmacology, University of Pittsburgh Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Assay Drug Dev Technol 5:737-50. 2007
    ..We also provide the structural basis for additional species-selective allosteric inhibitors of flaviviruses...
  6. ncbi request reprint Development and implementation of a 384-well homogeneous fluorescence intensity high-throughput screening assay to identify mitogen-activated protein kinase phosphatase-1 dual-specificity protein phosphatase inhibitors
    Paul A Johnston
    Pittsburgh Molecular Libraries Screening Center, Department of Pharmacology, University of Pittsburgh Drug Discovery Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA
    Assay Drug Dev Technol 5:319-32. 2007
    ....
  7. pmc Profiling the NIH Small Molecule Repository for compounds that generate H2O2 by redox cycling in reducing environments
    Karina M Soares
    Pittsburgh Molecular Library Screening Center, Drug Discovery Institute, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Assay Drug Dev Technol 8:152-74. 2010
    ....
  8. doi request reprint Implementation of a 220,000-compound HCS campaign to identify disruptors of the interaction between p53 and hDM2 and characterization of the confirmed hits
    Drew D Dudgeon
    University of Pittsburgh Drug Discovery Institute, School of Medicine, Pittsburgh, PA, USA
    J Biomol Screen 15:766-82. 2010
    ....
  9. pmc Development and validation of a high-content screening assay to identify inhibitors of cytoplasmic dynein-mediated transport of glucocorticoid receptor to the nucleus
    Paul A Johnston
    School of Medicine, University of Pittsburgh Drug Discovery Institute, Pittsburgh, Pennsylvania, USA
    Assay Drug Dev Technol 10:432-56. 2012
    ....
  10. ncbi request reprint Synthesis and biological activity of a focused library of mitogen-activated protein kinase phosphatase inhibitors
    David M Arnold
    Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Chem Biol Drug Des 69:23-30. 2007
    ....
  11. pmc Characterization and optimization of a novel protein-protein interaction biosensor high-content screening assay to identify disruptors of the interactions between p53 and hDM2
    Drew D Dudgeon
    Drug Discovery Institute, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Assay Drug Dev Technol 8:437-58. 2010
    ..Further, their corresponding cellular images and quantitative HCS data did not completely match the Nutlin-3 phenotypic profile...
  12. ncbi request reprint A case study from the chemistry core of the Pittsburgh Molecular Library Screening Center: the Polo-like kinase polo-box domain (Plk1-PBD)
    Peter Wipf
    Pittsburgh Molecular Library Screening Center, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Curr Top Med Chem 9:1194-205. 2009
    ..This case study highlights our development of a synthesis of 6-position functionalized uracil analogs, but also illustrates the importance of careful quality and compound stability monitoring of screening collections...
  13. pmc High-content pSTAT3/1 imaging assays to screen for selective inhibitors of STAT3 pathway activation in head and neck cancer cell lines
    Paul A Johnston
    1 Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania
    Assay Drug Dev Technol 12:55-79. 2014
    ..These data illustrate the power of a chemical biology approach to lead generation that utilizes fully developed and optimized HCS assays as phenotypic screens to interrogate specific signaling pathways...
  14. doi request reprint Identifying actives from HTS data sets: practical approaches for the selection of an appropriate HTS data-processing method and quality control review
    Tong Ying Shun
    University of Pittsburgh Drug Discovery Institute, Pittsburgh, PA, USA
    J Biomol Screen 16:1-14. 2011
    ..Step 3 is to apply the established active criterion to the quality-assured data to identify the active compounds...
  15. pmc Automated high-content live animal drug screening using C. elegans expressing the aggregation prone serpin α1-antitrypsin Z
    Sager J Gosai
    Department of Pediatrics, Cell Biology and Physiology, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh of UPMC and Magee Womens Hospital Research Institute, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 5:e15460. 2010
    ..This study provides powerful validation for advancement in preclinical drug discovery campaigns by screening live C. elegans modeling α1-antitrypsin deficiency and other complex disease phenotypes on high-content imaging platforms...
  16. pmc Characterization of inhibitors of glucocorticoid receptor nuclear translocation: a model of cytoplasmic dynein-mediated cargo transport
    Hikmat N Daghestani
    Department of Structural Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    Assay Drug Dev Technol 10:46-60. 2012
    ..Although the hits from the cell-based screen of the LOPAC-1280 collection did not exhibit this desired profile, this screening platform provided a promising phenotypic system for the discovery of dynein/HSP modulators...
  17. ncbi request reprint An interview with Paul A. Johnston, Ph.D., by Vicki Glaser
    Paul A Johnston
    Department of Pharmacology, University of Pittsburgh Drug Discovery Institute, School of Medicine, Pittsburgh, PA, USA
    Assay Drug Dev Technol 5:289-97. 2007
  18. pmc STAT3 signaling: anticancer strategies and challenges
    Paul A Johnston
    School of Pharmaceutical Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Mol Interv 11:18-26. 2011
    ..We review approaches that have been pursued to target STAT3, and we highlight some of the promises and challenges associated with developing an anticancer drug that might therapeutically inhibit the STAT3 signaling pathway...
  19. pmc Effector kinase coupling enables high-throughput screens for direct HIV-1 Nef antagonists with antiretroviral activity
    Lori A Emert-Sedlak
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
    Chem Biol 20:82-91. 2013
    ..Coupling of nonenzymatic viral accessory factors to host cell effector proteins amenable to high-throughput screening may represent a general strategy for the discovery of new antimicrobial agents...
  20. pmc Computational design, synthesis and biological evaluation of para-quinone-based inhibitors for redox regulation of the dual-specificity phosphatase Cdc25B
    Shahar Keinan
    Department of Chemistry, Duke University, Durham, NC, USA
    Org Biomol Chem 6:3256-63. 2008
    ..In contrast to a published hypothesis, the biological activities and hydrogen peroxide generation in reducing media of three synthetic models did not correlate with the quinone half-wave potential, E(1/2)...
  21. ncbi request reprint Generation and characterization of a stable MK2-EGFP cell line and subsequent development of a high-content imaging assay on the Cellomics ArrayScan platform to screen for p38 mitogen-activated protein kinase inhibitors
    Rhonda Gates Williams
    Sphinx RTP Laboratories, Eli Lilly and Company, Research Triangle Park, NC, USA
    Methods Enzymol 414:364-89. 2006
    ..An example of mining "high-content" image-based multiparameter data to extract additional information on the effects of compound treatment of cells is presented...
  22. ncbi request reprint Development and implementation of three mitogen-activated protein kinase (MAPK) signaling pathway imaging assays to provide MAPK module selectivity profiling for kinase inhibitors: MK2-EGFP translocation, c-Jun, and ERK activation
    Debra Nickischer
    Sphinx RTP Laboratories, Eli Lilly and Company, Research Triangle Park, NC, USA
    Methods Enzymol 414:389-418. 2006
    ..However, selective MAPK inhibitors were identified that exhibited pathway selectivity as evidenced by significantly lower IC(50) values for their respective p38, JNK, or ERK signaling pathway assays...
  23. ncbi request reprint Configuring radioligand receptor binding assays for HTS using scintillation proximity assay technology
    John W Carpenter
    Sphinx Laboratories, Eli Lilly and Company, Research Triangle Park, NC, USA
    Methods Mol Biol 190:31-49. 2002
  24. ncbi request reprint Assay development and case history of a 32K-biased library high-content MK2-EGFP translocation screen to identify p38 mitogen-activated protein kinase inhibitors on the ArrayScan 3.1 imaging platform
    Oscar J Trask
    Sphinx RTP Laboratories, Eli Lilly and Company, Research Triangle Park, NC, USA
    Methods Enzymol 414:419-39. 2006
    ..Three of the hit scaffolds identified in the MK2-EGFP translocation HCS run on the ArrayScan were selected for a p38a inhibitor hit-to-lead structure activity relationship (SAR) chemistry effort...
  25. ncbi request reprint Cellular platforms for HTS: three case studies
    Paul A Johnston
    Sphinx Laboratories, Lilly Research Laboratories, A Division of Eli Lilly and Company, 20 T W Alexander Drive, PO Box 13951, Research Triangle Park, NC 27709, USA
    Drug Discov Today 7:353-63. 2002
    ..In this review, we describe three case studies in which targets were successfully interrogated in cell-based HTS, and highlight the necessary steps to ensure the validity of these screens...