High concentration electrophysiology-based fragment screen: Discovery of novel acid-sensing ion channel 3 (ASIC3) inhibitors

Scott E. Wolkenberg, Zhijian Zhao, James J. Mulhearn, Scott T. Harrison, John M. Sanders, Matthew J. Cato, Aneta Jovanovska, Jacqueline Panigel, Sean P. Cook, Darrell A. Henze, Stefanie A. Kane, George D. Hartman, James C. Barrow

Research output: Contribution to journalArticle

Abstract

The Merck Fragment Library was screened versus acid-sensing ion channel 3 (ASIC3), a novel target for the treatment of pain. Fragment hits were optimized using two strategies, and potency was improved from 0.7 mM to 3 μM with retention of good ligand efficiency and incorporation of reasonable physical properties, off-target profile, and rat pharmacokinetics.

Original languageEnglish (US)
Pages (from-to)2646-2649
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number9
DOIs
StatePublished - May 1 2011
Externally publishedYes

Keywords

  • Acid-sensing ion channel 3
  • Electrophysiology
  • Fragment screening

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Wolkenberg, S. E., Zhao, Z., Mulhearn, J. J., Harrison, S. T., Sanders, J. M., Cato, M. J., Jovanovska, A., Panigel, J., Cook, S. P., Henze, D. A., Kane, S. A., Hartman, G. D., & Barrow, J. C. (2011). High concentration electrophysiology-based fragment screen: Discovery of novel acid-sensing ion channel 3 (ASIC3) inhibitors. Bioorganic and Medicinal Chemistry Letters, 21(9), 2646-2649. https://doi.org/10.1016/j.bmcl.2010.12.115