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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. ✖ |
| 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 | ||||||||||||||||||||||||||||||||||
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| Ligand mentioned in the following text fields |
| Calcitonin receptors overview |
