A µ-Opioid Receptor Modulator that Works Cooperatively with Naloxone

G-protein coupled receptors (GPCRs) play a pivotal role in signaling pathways, and these transmembrane proteins represent an important drug target class. The majority of approved drugs that target GPCRs bind to traditional orthosteric sites. In a recent publication in Nature, Professor Brian Kobilka and his team at Stanford University successfully identified selective negative allosteric modulators (NAMs) for the μ-opioid receptor (μOR) using DNA-encoded library (DEL) technology.

The compound, 368, was discovered directly from WuXi AppTec’s DEL product and exhibited permeability across the blood-brain barrier, as well as efficacy in both in vitro and in vivo models without any modifications. This work exemplifies an effective application of DEL technology in identifying novel hits for GPCR targets.