Premium
Non‐peptide agonists and positive allosteric modulators of glucagon‐like peptide‐1 receptors: Alternative approaches for treatment of Type 2 diabetes
Author(s) -
Malik Faisal,
Li Zhijun
Publication year - 2022
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.15446
Subject(s) - receptor , allosteric regulation , g protein coupled receptor , peptide , incretin , glucagon like peptide 1 , pharmacology , allosteric modulator , chemistry , biology , biochemistry , type 2 diabetes , endocrinology , diabetes mellitus
Glucagon-like peptide-1 (GLP-1) receptors belong to the pharmaceutically important Class B family of GPCRs and are involved in many biologically significant signalling pathways. Its incretin peptide ligand GLP-1 analogues are effective treatments for Type 2 diabetes. Although developing non-peptide low MW drugs targeting GLP-1 receptors remains elusive, considerable progress has been made in discovering non-peptide agonists and positive allosteric modulators (PAMs) of GLP-1 receptors with demonstrated efficacy. Many of these compounds induce biased signalling in GLP-1 receptor-mediated functional pathways. High-quality structures of GLP-1 receptors in both inactive and active states have been reported, revealing detailed molecular interactions between GLP-1 receptors and non-peptide agonists or PAMs. These progresses raise the exciting possibility of developing non-peptide drugs of GLP-1 receptors as alternative treatments for Type 2 diabetes. The insight into the interactions between the receptor and the non-peptide ligand is also useful for developing non-peptide ligands targeting other Class B GPCRs. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.