Discovery of Small Molecule Kappa Opioid Receptor Agonist and Antagonist Chemotypes through a HTS and Hit Refinement Strategy.

Journal Article (Journal Article)

Herein we present the outcome of a high throughput screening (HTS) campaign-based strategy for the rapid identification and optimization of selective and general chemotypes for both kappa (κ) opioid receptor (KOR) activation and inhibition. In this program, we have developed potent antagonists (IC(50) < 120 nM) or agonists of high binding affinity (K(i) < 3 nM). In contrast to many important KOR ligands, the compounds presented here are highly modular, readily synthesized and, in most cases, achiral. The four new chemotypes hold promise for further development into chemical tools for studying the KOR or as potential therapeutic lead candidates.

Full Text

Duke Authors

Cited Authors

  • Frankowski, KJ; Hedrick, MP; Gosalia, P; Li, K; Shi, S; Whipple, D; Ghosh, P; Prisinzano, TE; Schoenen, FJ; Su, Y; Vasile, S; Sergienko, E; Gray, W; Hariharan, S; Milan, L; Heynen-Genel, S; Mangravita-Novo, A; Vicchiarelli, M; Smith, LH; Streicher, JM; Caron, MG; Barak, LS; Bohn, LM; Chung, TDY; Aubé, J

Published Date

  • March 21, 2012

Published In

Volume / Issue

  • 3 / 3

Start / End Page

  • 221 - 236

PubMed ID

  • 22737280

Pubmed Central ID

  • PMC3378255

Electronic International Standard Serial Number (EISSN)

  • 1948-7193

Digital Object Identifier (DOI)

  • 10.1021/cn200128x


  • eng

Conference Location

  • United States