Clinical data
Routes of
ATC code none
CAS Number 698387-09-6 N
PubChem (CID) 9915743
ChemSpider 8091392 YesY
KEGG D08950 YesY
Chemical and physical data
Formula C30H29ClN6O3
Molar mass 557.04 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

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

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

Mechanism of action

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

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.[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

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