Neratinib (maleate)

Neratinib (HKI-272) maleate is an orally available, irreversible, highly selective HER2 and EGFR inhibitor with IC₅₀s of 59 nM and 92 nM, respectively^[1]. In Vitro: Neratinib displays no activity against other serine-threonine kinases such as Akt, cyclin D1/cdk4, cyclin E/cdk2, cyclin B1/cdk1, IKK-2, MK-2, PDK1, c-Raf, and Tpl-2, as well as the tyrosine kinase c-Met^[1].
Neratinib (0.5 ng/mL–5 μg/mL, 2 days) inhibits the proliferation of cell lines that show high levels of HER-2 (3T3/neu, SK-Br-3, and BT474) and is much less active in cell lines that express neither HER-2 nor EGFR (3T3, MDA-MB-435, and SW620) ^[1].
Neratinib (0-2 nM, 12-16 h) arrests BT474 cell cycle at G1-S phase^[1].
Neratinib results in the inhibition of MAPK and Akt phosphorylation, down-regulation of cyclin D1 levels, and induction of p27^[1]. In Vivo: Neratinib (HKI-272) (0-80 mg/kg/day; i.g.; 42 days) shows anticancer activities against cancer cells that expresses high levels of HER-2 or EGFR^[1].