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December 2016

Neratinib in ERBB2-Positive Brain Metastases

Author Affiliations
  • 1Stanford School of Medicine, Stanford Womens Cancer Center, Stanford, California

Copyright 2016 American Medical Association. All Rights Reserved.

JAMA Oncol. 2016;2(12):1541-1543. doi:10.1001/jamaoncol.2016.0238

Neratinib was originally derived by modication of EKB-569 (pelitinib), an irreversible epidermal growth factor receptor (EGFR) inhibitor. Like other irreversible ERBB family tyrosine kinase inhibitors (TKIs), the chemistry of neratinib is based on a quinolone core with a Michael acceptor moiety designed to form a covalent bond with the conserved cysteine residues at the adenosine triphosphate (ATP) binding sites (Cys-773 and Cys-805) in EGFR and ERBB2 (formerly HER2 or HER2/neu), respectively, resulting in IC50 values of 92nM for EGFR and 59nM for the ERBB2 kinase.1