Discovery of a First-In-Class Small Molecule Antagonist against the Adrenomedullin-2 Receptor: Structure-Activity Relationships and Optimization.

ABSTRACT: Class B G-protein-coupled receptors (GPCRs) remain an underexploited target for drug development. The calcitonin receptor (CTR) family is particularly challenging, as its receptors are heteromers comprising two distinct components: the calcitonin receptor-like receptor (CLR) or calcitonin receptor (CTR) together with one of three accessory proteins known as receptor activity-modifying proteins (RAMPs). CLR/RAMP1 forms a CGRP receptor, CLR/RAMP2 forms an adrenomedullin-1 (AM₁) receptor, and CLR/RAMP3 forms an adrenomedullin-2 (AM₂) receptor. The CTR/RAMP complexes form three distinct amylin receptors. While the selective blockade of AM₂ receptors would be therapeutically valuable, inhibition of AM₁ receptors would cause clinically unacceptable inc

SUBMITTER: Zirimwabagabo JO 

PROVIDER: S-EPMC8006142 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature