The calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide distributed widely through the peripheral and central nervous systems which has been implicated in the pathogenesis of migraine.  Blocking function with antibodies that bind CGRP, CGRP receptor antibodies, and small molecule antagonists have all demonstrated clinical efficacy for the treatment of migraine, although the peripheral or central site of action for these agents is debatable.  A positron emission tomography (PET) tracer was developed in order to determine the central target engagement of small molecule antagonists binding to the CGRP receptor, a heterodimer consisting of the calcitonin-like receptor (CLR, a G protein-coupled receptor), and an accessory protein, receptor activity modifying protein 1 (RAMP1).  This presentation will outline the discovery, preclinical data package, and non-human primate validation of an [<sup>18</sup>F]-radiolabelled small molecule antagonist of CGRP as a PET tracer and its utility in driving a drug discovery effort.<br/>

Discovery and application of a calcitonin gene-related peptide (CGRP) receptor antagonist as a positron emission tomography (PET) ligand for the determination of central target engagement

ACS Fall 2020 Virtual Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.