|
Synonyms: ALD-403 | ALD403 | eptinezumab-jjmr | Vyepti®
eptinezumab is an approved drug (FDA (2020), EMA (2022))
Compound class:
Antibody
Comment: Eptinezumab is a humanized IgG1 anti-calcitonin gene-related peptide (CGRP) monoclonal antibody for the prevention of migraine [6]. It was developed by Lundbeck and their subsidiary Alder Biopharmaceuticals (Alderbio). The INN record for eptinezumab indicates that it binds to CALCA (α-CGRP) and CALCB (β-CGRP). Peptide sequence alignment using NCBI BLAST Protein reveals 100% matches with sequences claimed in Alderbio's patent WO2012162257A2, and distinguish eptinezumab as the monoclonal referred to as Ab5 in the patent document.
CGRP plays an important role in migraine pathophysiology [2], and both the CGRP peptide and its receptor (CGRPR) are targets of anti-migraine therapeutics [1,4-5]. Eptinezumab is the fourth anti-CGRP pathway monoclonal to reach the clinic: the others are erenumab (anti-CGRPR), galcanezumab (anti-CALCA/B) and fremanezumab (anti-CALCA/B). These antibodies are used as alternatives to CGRPR antagonists such as ubrogepant (FDA approved in 2019). |
| Bioactivity Comments |
| Monoclonal Ab5 inhibits α-CGRP-induced cAMP elevation via the CGRPR in human neuroepithelioma SK-N-MC cells with an IC50 of 0.4 nM [3]. The comparable IC50 value for β-CGRP-induced cAMP production is 0.88 nM. Ab5 inhibits binding of 125I-labelled α-CGRP to recombinant human CGRP receptors with a Ki of 0.46 nM in a membrane binding assay. |
| Selectivity at ligand targets | ||||||||||||||||||||||||||||||||||
| Key to terms and symbols | Click column headers to sort | |||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
