Work

Rational Design Biased Compounds against μ-Opioid Receptor

Year: 2025

Type: article

Abstract: Agonists targeting the μ-opioid receptor (MOR) are the most effective analgesics, but their clinical use is limited by adverse side effects which are partly induced by β-arrestin signaling. Here, we combined in silico methods and cell-based functional assays to design novel structural scaffold molecules with high affinity that were biased at the G protein signaling of MOR. Furthermore, we explored the molecular mechanism of G protein subtype preference via computational methods. The results of our studies provide an insightful view into the ligand-MOR binding mode, which could serve as an important guide for the design of next-generation MOR ligands with reduced side effects.

Source: ACS Pharmacology & Translational Science

DOI: 10.1021/acsptsci.5c00055

Authors: Chenyang Wu, Yi Li, Horst Vogel, Shuguang Yuan

Institutions: Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology, University of Chinese Academy of Sciences, Shenzhen University of Advanced Technology, École Polytechnique Fédérale de Lausanne

Language: English

Topic: Receptor Mechanisms and Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W4409241952

FWCI: 0.756

Cites: 41

Cited by: 3

Related to: 10