Neratinib

Neratinib is a cell-permable, irreversible, selective inhibitor of the HER2 kinase (IC50=59nM) and EGFR (IC50=92nM) by preventing phosphorylation of these proteins by their respective kinases. It also potently inhibits several mutants of HER2 and shows 10-fold or greater selectivity over a wide variety of other kinases. As an irreversible inhibitor, neratinib may circumvent acquired resistance developed against reversible inhibitors, including gefitinib. Neratinib displays activity against a variety of cancer cell lines, including A431, 3T3, and MDA-MB-435. Neratinib has been evaluated in clinical trials against cancers characterized by HER2 overexpression or HER2 activating mutations. Product References: (1) S.K. Rabindran, et al., Cancer Res. 64, 3958 (2004) , (2) E.L. Kwak, et al., PNAS 102, 7665 (2005) , (3) H. Ji, et al., PNAS 103, 7817 (2006) , (4) P. Bose & H. Ozer, Expert. Opin. Investig. Drugs 18, 1735 (2009) (Review) , (5) M.I. Davis, et al., Nat. Biotechnol. 29, 1046 (2011) , (6) S.M. Kavuri, et al., Cancer Discov. 5, 832 (2015) , (7) M. Segovia-Mendoza, et al., Am. J. Cancer Res. 5, 2531 (2015) , (8) S.R. Tiwari, et al., Clin. Breast Cancer 16, 344 (2016) (Review) Appearance: Off-white powder. Solubility: Soluble in DMSO (2mg/ml). Insoluble in water. Identity: Determined by 1H-NMR. InChi Key: JWNPDZNEKVCWMY-VQHVLOKHSA-N Smiles: CCOC1=C(NC(/C=C/CN(C)C)=O)C=C(C(NC2=CC(Cl)=C(OCC3=NC=CC=C3)C=C2)=C(C#N)C=N4)C4=C1