|
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 fully human 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 is used clinically to prevent migraine headache. The selectivity of erenumab for the CGRPR vs. the AMY1 receptor has not been fully established.
Anti-CGRPR antagonistic monoclonals are being developed in place of non-peptide small molecule CGRPR antagonists as these have suffered from hepatotoxicity liability (although this has been largely overcome by using different chemotypes) 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]. 
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
| References |
|
1. A-González N, Castrillo A. (2011)
Liver X receptors as regulators of macrophage inflammatory and metabolic pathways. Biochim Biophys Acta, 1812 (8): 982-94. [PMID:21193033] |
|
2. Dodick DW, Ashina M, Brandes JL, Kudrow D, Lanteri-Minet M, Osipova V, Palmer K, Picard H, Mikol DD, Lenz RA. (2018)
ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia, 38 (6): 1026-1037. [PMID:29471679] |
|
3. Edvinsson L. (2018)
The CGRP Pathway in Migraine as a Viable Target for Therapies. Headache, 58 Suppl 1: 33-47. [PMID:29697153] |
|
4. Edvinsson L, Haanes KA, Warfvinge K, Krause DN. (2018)
CGRP as the target of new migraine therapies - successful translation from bench to clinic. Nat Rev Neurol, 14 (6): 338-350. [PMID:29691490] |
|
5. Hansen JM, Hauge AW, Olesen J, Ashina M. (2010)
Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia, 30 (10): 1179-86. [PMID:20855363] |
|
6. Paemeleire K, MaassenVanDenBrink A. (2018)
Calcitonin-gene-related peptide pathway mAbs and migraine prevention. Curr Opin Neurol, 31 (3): 274-280. [PMID:29432219] |
|
7. Shi L, Lehto SG, Zhu DX, Sun H, Zhang J, Smith BP, Immke DC, Wild KD, Xu C. (2016)
Pharmacologic Characterization of AMG 334, a Potent and Selective Human Monoclonal Antibody against the Calcitonin Gene-Related Peptide Receptor. J Pharmacol Exp Ther, 356 (1): 223-31. [PMID:26559125] |
|
8. Sun H, Dodick DW, Silberstein S, Goadsby PJ, Reuter U, Ashina M, Saper J, Cady R, Chon Y, Dietrich J et al.. (2016)
Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol, 15 (4): 382-90. [PMID:26879279] |
