1 research outputs found
Discovery of Small Molecule Kappa Opioid Receptor Agonist and Antagonist Chemotypes through a HTS and Hit Refinement Strategy
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<sub>50</sub> < 120 nM) or agonists
of high binding affinity (<i>K</i><sub>i</sub> < 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