Identification of Small-Molecule Positive Modulators of Calcitonin-like Receptor-Based Receptors.

ABSTRACT: Class B G protein-coupled receptors are highly therapeutically relevant but challenges remain in identifying suitable small-molecule drugs. The calcitonin-like receptor (CLR) in particular is linked to conditions such as migraine, cardiovascular disease, and inflammatory bowel disease. The CLR cannot act as a cell-surface receptor alone but rather must couple to one of three receptor activity-modifying proteins (RAMPs), forming heterodimeric receptors for the peptides adrenomedullin and calcitonin gene-related peptide. These peptides have extended binding sites across their receptors. This is one reason why there are few small-molecule ligands that can modulate these receptors. Here we describe small molecules that are able to positively modulate the signaling of the CLR with all three RAM

SUBMITTER: Hendrikse ER 

PROVIDER: S-EPMC7155196 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature