Discovery of μ,δ-Opioid Receptor Dual-Biased Agonists That Overcome the Limitation of Prior Biased Agonists.

ABSTRACT: Morphine is widely used in pain management although the risk of side effects is significant. The use of biased agonists to the G protein of μ-opioid receptors has been suggested as a potential solution, although oliceridine and PZM21 have previously failed to demonstrate benefits in clinical studies. An amplification-induced confusion in the process of comparing G protein and beta-arrestin pathways may account for previously biased agonist misidentification. Here, we have devised a strategy to discover biased agonists with intrinsic efficacy. We computationally simulated 430 000 molecular dockings to the μ-opioid receptor to construct a compound library. Hits were then verified experimentally. Using the verified compounds, we performed simulations to build a second library with a common sc

SUBMITTER: Lee JH 

PROVIDER: S-EPMC8204323 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature