Neratinib (HKI-272) is an orally-available, quinazoline-based, irreversible inhibitor of HER-2 and EGFR kinases, with IC50 values of 59 and 92 nM, respectively. [1] Neratinib treatment in cells results in expected downstream inactiviation of signal transduction events, leading to cell cycle arrest at the G1-S-phase transition. [2] Neratninb is selective over a broad range of serine-threonine and receptor tyrosine kinases. In cell proliferation assays, Neratinib inhibits mouse fibroblast cell lines (3T3) transfected with HER-2 at and IC50 of 3 nM. Additionally, inhibition of other HER-2- or EGFR-overexpressing celll lines such as SK-Br-3, BT474, and A431 was shown to be at IC50s of 2, 2, and 81 nM, respectively. [2]

Neratinib effectively inhibits phosphorylation of BT474, MPAK, and Akt at concentrations of 5, 2, and 2 nM, respectively. Phase I trials have shown that Neratinib can achieve stable disease control for over 6 months in NSCLC that has progressed after treatment with gefitinib or erlotinib. [3]

Neratinib (HKI-272) is an orally-available, quinazoline-based, irreversible inhibitor of HER-2 and EGFR kinases, with IC50 values of 59 and 92 nM, respectively. [1] Neratinib treatment in cells results in expected downstream inactiviation of signal transduction events, leading to cell cycle arrest at the G1-S-phase transition. [2] Neratninb is selective over a broad range of serine-threonine and receptor tyrosine kinases. In cell proliferation assays, Neratinib inhibits mouse fibroblast cell lines (3T3) transfected with HER-2 at and IC50 of 3 nM. Additionally, inhibition of other HER-2- or EGFR-overexpressing celll lines such as SK-Br-3, BT474, and A431 was shown to be at IC50s of 2, 2, and 81 nM, respectively. [2]

Neratinib effectively inhibits phosphorylation of BT474, MPAK, and Akt at concentrations of 5, 2, and 2 nM, respectively. Phase I trials have shown that Neratinib can achieve stable disease control for over 6 months in NSCLC that has progressed after treatment with gefitinib or erlotinib. [3]