|Chemical and physical data|
|Molar mass||557.04 g/mol|
|3D model (Jmol)|
|(what is this?)|
Mechanism of action
Neratinib inhibits the epidermal growth factor receptor by covalently binding with a cysteine side chain in that protein.
Biological Activity of Neratinib
Neratinib(HKI-272) IC50,respectively, 59, nM, HER2 and epidermal growth factor receptor available and irreversible tyrosine kinase inhibitors. In vivo:Neratinib weakly inhibition of tyrosine kinase KDR and Src, IC50 were 0.8 um and 1.4 um, respectively, being 14- and 24-fold less active compared with HER2. Neratinib for BT474 cells, mainly used to reduce the HER2 receptor autophosphorylation and IC50 were used to reduce the proliferation of A431 cells of 5 nm and 3 nM.Neratinib for BT474 cells and inhibition of cyclin D1 expression of phosphorylated and Rb-Rb- sensitivity of gene product phosphorylation and IC50 for 9 nm, and reduced cell proliferation is reduced, so as to make a cell cycle arrest in G1. In vivo: Neratinib was administered orally at doses of 10, 20,, 40, and 80mg/kg, each day, to inhibit the growth of 3T3/neu transplanted tumors. At the same time, the daily dose of Neratinib was 5 and 60mg/kg, which could significantly inhibit the growth of SK-OV-3 transplanted tumor.
- "Definition of neratinib - National Cancer Institute Drug Dictionary". Retrieved 2008-12-01.
- Rabindran SK, Discafani CM, Rosfjord EC, et al. (June 2004). "Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase". Cancer Res. 64 (11): 3958–65. doi:10.1158/0008-5472.CAN-03-2868. PMID 15173008.
- Clinical trial number NCT00398567 for "A Phase 1/2 Study Of HKI-272 In Combination With Herceptin In Subjects With Advanced Breast Cancer" at ClinicalTrials.gov
- "Puma Acquires Global Rights to Pfizer's Phase III Breast Cancer Drug Neratinib".
- Minami Y, Shimamura T, Shah K, et al. (July 2007). "The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272". Oncogene. 26 (34): 5023–7. doi:10.1038/sj.onc.1210292. PMID 17311002.
- http://www.reuters.com/article/idUSN1612347120100317 "Breast cancer study aims to speed drugs, cooperation" March 2010