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Neratinib skeletal.svg
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Chemical and physical data
Formula C30H29ClN6O3
Molar mass 557.04 g/mol
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Neratinib (HKI-272) is a tyrosine kinase inhibitor[1][2] under investigation for the treatment of breast cancer[3] and other solid tumours.

It is in development for the treatment of early- and late-stage HER2-positive breast cancer.[4]

Like lapatinib and afatinib, it is a dual inhibitor of the human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) kinases.[5]

Clinical trials[edit]

Neratanib is being developed by Puma Biotechnology. It will be included in the forthcoming I-SPY2 breast cancer trial.[6]

Mechanism of action[edit]

Neratinib inhibits the epidermal growth factor receptor by covalently binding with a cysteine side chain in that protein.[7]

Biological Activity of Neratinib[edit]

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.[8]


  1. ^ "Definition of neratinib - National Cancer Institute Drug Dictionary". Retrieved 2008-12-01. 
  2. ^ 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. 
  3. ^ Clinical trial number NCT00398567 for "A Phase 1/2 Study Of HKI-272 In Combination With Herceptin In Subjects With Advanced Breast Cancer" at
  4. ^ "Puma Acquires Global Rights to Pfizer's Phase III Breast Cancer Drug Neratinib". 
  5. ^ 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. 
  6. ^ "Breast cancer study aims to speed drugs, cooperation" March 2010
  7. ^
  8. ^