Neratinib

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Neratinib
Neratinib skeletal.svg
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
Legal status
?
Routes Oral
Identifiers
CAS number 698387-09-6 N
ATC code None
PubChem CID 9915743
ChemSpider 8091392 YesY
UNII JJH94R3PWB YesY
KEGG D08950 YesY
ChEMBL CHEMBL180022 YesY
Chemical data
Formula C30H29ClN6O3 
Mol. mass 557.04 g/mol
 N (what is this?)  (verify)

Neratinib (HKI-272) is a tyrosine kinase inhibitor[1][2] under investigation for the treatment 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]

References[edit]

  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. ^ ClinicalTrials.gov NCT00398567 A Phase 1/2 Study Of HKI-272 In Combination With Herceptin In Subjects With Advanced Breast Cancer
  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