Neratinib inhibited the kinase acti

Neratinib inhibited the kinase activity of HER2 and EGFR at IC50 values of 59 nM and 92 nM, respectively, in studies conducted by the Applicant. In another study reported in the literature, neratinib inhibited the activity of HER2 (IC50 = 39 nM), EGFR (IC50 =12 nM) and HER4 (IC50 = 19 nM) in a phosphorylation assay (Davis, Hunt, et al. 20111). The kinase activity of neratinib was evaluated using a panel of recombinant serine-threonine kinases (Akt, cyclin D1/cdk4, cyclin E/cdk2, cyclin B1/cdk1, IKK-2, MK-2, PDK1, c-Raf, Tpl-2) or cMET. The results show that neratinib inhibited HER2 and EGFR phosphorylation at IC50 values of 59 nM and 92nM, respectively. Further, neratinib did not inhibit or caused weak inhibition of other tyrosine kinases (IC50’s ≥ 8 fold over EGFR), suggesting specificity of neratinib for HER2 and EGFR.