Neratinib (HKI-272)

- Overview
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    Background
    
    IC50: 59 nM (Her-2); 92 nM (EGFR)HER-2 belongs to the ErbB family of receptor tyrosine kinases, which has been implicated in a variety of cancers. Overexpression of HER-2 is seen in 25–30% of breast cancer patients and predicts a poor outcome in patients with primary disease. Neratinib (HKI-272) is a tyrosine kinase inhibitor under investigation for the treatment breast cancer and other solid tumours.In vitro: Neratinib (HKI-272) is a potent inhibitor of HER-2 and is highly active against HER-2-overexpressing human breast cancer cell lines in vitro. It also inhibits the epidermal growth factor receptor (EGFR) kinase and the proliferation of EGFR-dependent cells. Neratinib reduces HER-2 receptor autophosphorylation in cells at doses consistent with inhibition of cell proliferation and functions as an irreversible binding inhibitor, most likely by targeting a cysteine residue in the ATP-binding pocket of the receptor. In agreement with the predicted effects of HER-2 inactivation, Neratinib treatment of cells results in inhibition of downstream signal transduction events and cell cycle regulatory pathways. This leads to arrest at the G1-S (Gap 1/DNA synthesis)-phase transition of the cell division cycle, ultimately resulting in decreased cell proliferation [1].In vivo: In vivo, Neratinib is active in HER-2- and EGFR-dependent tumor xenograft models when dosed orally on a once daily schedule. On the basis of its favorable preclinical pharmacological profile, Neratinib has been selected as a candidate for additional development as an antitumor agent in breast and other HER-2-dependent cancers [1].Clinical trial: Neratinib is in development for the treatment of early- and late-stage HER2-positive breast cancer. Neratanib is being developed by Puma Biotechnology. It will be included in the forthcoming I-SPY2 breast cancer trial (http://en.wikipedia.org/wiki/Neratinib).
- Properties
  - Alternative Name
    
    HKI-272;HKI272;HKI 272; (E)-N-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide
    
    CAS Number
    
    698387-09-6
    
    Molecular Formula
    
    C30H29ClN6O3
    
    Molecular Weight
    
    557.04
    
    Appearance
    
    A solid
    
    Purity
    
    98.58%
    
    Solubility
    
    insoluble in H2O; ≥13.93 mg/mL in DMSO with gentle warming; ≥2.52 mg/mL in EtOH with gentle warming
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only
- Reference
  - 1. Duggan BM, Foley KP, et al."Tyrosine kinase inhibitors of Ripk2 attenuate bacterial cell wall-mediated lipolysis, inflammation and dysglycemia." Sci Rep. 2017 May 8;7(1):1578. PMID:28484277

Neratinib (HKI-272)

Background

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