Neratinib

Neratinib

Systematic (IUPAC) name
(2E)-N-[4-[[3-chloro-4-[(pyridin-2-yl)methoxy]phenyl]amino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide
Clinical data
Routes of administration	Oral
Identifiers
CAS Number	698387-09-6
ATC code	None
PubChem	CID 9915743
IUPHAR/BPS	5686
ChemSpider	8091392
UNII	JJH94R3PWB
KEGG	D08950
ChEMBL	CHEMBL180022
Chemical data
Formula	C30H29ClN6O3
Molar mass	557.04 g/mol
SMILES O=C(/C=C/CN(C)C)Nc4cc1c(ncc(C#N)c1Nc3ccc(OCc2ncccc2)c(Cl)c3)cc4OCC
InChI InChI=1S/C30H29ClN6O3/c1-4-39-28-16-25-23(15-26(28)36-29(38)9-7-13-37(2)3)30(20(17-32)18-34-25)35-21-10-11-27(24(31)14-21)40-19-22-8-5-6-12-33-22/h5-12,14-16,18H,4,13,19H2,1-3H3,(H,34,35)(H,36,38)/b9-7+ Key:JWNPDZNEKVCWMY-VQHVLOKHSA-N
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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

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]

References

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 ClinicalTrials.gov
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. http://www.reuters.com/article/idUSN1612347120100317 "Breast cancer study aims to speed drugs, cooperation" March 2010
7. http://www.biomedicale.univ-paris5.fr/enseignement/toxico/M2THERV_2013_2014/documents/C15/DANSETTE/EH_CB_RM_M2/CovalentDrug_Baillie_nrd3410.pdf