2. Academic Validation
  3. High concentration electrophysiology-based fragment screen: discovery of novel acid-sensing ion channel 3 (ASIC3) inhibitors

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

  • Bioorg Med Chem Lett. 2011 May 1;21(9):2646-9. doi: 10.1016/j.bmcl.2010.12.115.
Scott E Wolkenberg 1,  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
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Research Laboratories, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA. scott_wolkenberg@merck.com
PMID: 21257308 DOI: 10.1016/j.bmcl.2010.12.115
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.

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