erenumab   

GtoPdb Ligand ID: 9250

Synonyms: Aimovig® | AMG 334 | AMG-334 | erenumab-aooe
erenumab is an approved drug (FDA & EMA (2018))
Compound class: Antibody
Comment: Erenumab (erenumab-aooe, AMG-334) is a first-in-class monoclonal antibody targeting the calcitonin gene-related peptide receptor (CGRPR) [7] (and the first approved GPCR targeted monoclonal). Antibody production was initiated by immunising mice with polypeptides from the N-terminal extracellular domains of human CRLR and human RAMP1, which are subunits of the CGRPR protein complex. Erenumab (a fully human monoclonal) is being a preventative treatment for adults suffering from migraine headache.

Anti-CGRPR antagonistic monoclonals are being developed in place of non-peptide small molecule CGRPR antagonists as these have suffered from hepatotoxicity liability when tested as migraine prophylactics. Antibodies have the positive attributes of being able to span the relatively large binding domain across the CGRPR complex to provide effective blockade, offer the potential for selectivity given the similarity with other receptors in the family, and exhibit a prolonged serum half-life which facilitates longer dosing intervals [1].
Bioactivity Comments
In functional in vitro cell-based assays AMG-334 abolishes CGRP-stimulated cAMP production (IC50 2.3nM), and is 5000-fold selective for the CGRP receptor over other human calcitonin family receptors [7]. AMG-334 has affinity for the cynomolgus monkey CGRP receptor similar to that for the human receptor, but has drastically reduced affinity for the dog, rabbit and rat receptors, excluding these latter species from providing preclinical testing models.
Selectivity at GPCRs
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
CGRP receptor Hs Antibody Antagonist 10.7 pKi - 7
pKi 10.7 (Ki 2x10-11 M) [7]
Description: Displacement binding of [(125)I]-CGRP at the human CGRP receptor