Discovery of the Migraine Prevention Therapeutic Aimovig (Erenumab), the First FDA-Approved Antibody against a G-Protein-Coupled Receptor.

Autor:	King CT; Amgen Research, 1 Amgen Center Drive, Thousand Oaks, California 91320-1799, United States., Gegg CV; Amgen Research, 1 Amgen Center Drive, Thousand Oaks, California 91320-1799, United States., Hu SN; Amgen Research, 1 Amgen Center Drive, Thousand Oaks, California 91320-1799, United States., Sen Lu H; Amgen Research, 1 Amgen Center Drive, Thousand Oaks, California 91320-1799, United States., Chan BM; Amgen Research, 1 Amgen Center Drive, Thousand Oaks, California 91320-1799, United States., Berry KA; Amgen Research, 1 Amgen Center Drive, Thousand Oaks, California 91320-1799, United States., Brankow DW; Amgen Research, 1 Amgen Center Drive, Thousand Oaks, California 91320-1799, United States., Boone TJ; Amgen Research, 1 Amgen Center Drive, Thousand Oaks, California 91320-1799, United States., Kezunovic N; Amgen Research, 1 Amgen Center Drive, Thousand Oaks, California 91320-1799, United States., Kelley MR; Amgen Research, 1 Amgen Center Drive, Thousand Oaks, California 91320-1799, United States., Shi L; Amgen Research, 1 Amgen Center Drive, Thousand Oaks, California 91320-1799, United States., Xu C; Amgen Research, 1 Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Jazyk:	angličtina
Zdroj:	ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2019 Sep 03; Vol. 2 (6), pp. 485-490. Date of Electronic Publication: 2019 Sep 03 (Print Publication: 2019).
DOI:	10.1021/acsptsci.9b00061
Abstrakt:	In 2018, the United States Food and Drug Administration (FDA) approved Aimovig (erenumab) for the prevention of migraine. Erenumab is the first FDA approved antibody therapeutic against a G-protein-coupled receptor, the canonical receptor of calcitonin gene related peptide (CGRP-R). A novel, epitope-focused antigen was created to reconstruct the extracellular domains of the CGRP-R in a stable conformation. Successful inoculation of XenoMouse animals and careful screening yielded multiple candidate molecules for high potency and exquisite selectivity toward the CGRP-R over related receptors. These efforts led to the discovery of erenumab which has demonstrated the desired efficacy and safety profiles in multiple clinical studies for the prevention of migraine. The innovation developed in the discovery of erenumab furthers the ability to target G-coupled protein receptors using antibody approaches. Competing Interests: The authors declare the following competing financial interest(s): All authors are or were employed by Amgen Inc. (Copyright © 2019 American Chemical Society.)
Databáze:	MEDLINE
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