Routes of
administration Oral CAS Number 698387-09-6 IUPHAR/BPS 5686 Molar mass 557.04 g/mol | ATC code none PubChem CID 9915743 ChemSpider 8091392 | |
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Neoadjuvant therapy with neratinib plus trastuzumab in locally advanced her2 positive breast cancer
Neratinib (HKI-272) is a tyrosine kinase inhibitor under investigation for the treatment of breast cancer and other solid tumours.
Contents
- Neoadjuvant therapy with neratinib plus trastuzumab in locally advanced her2 positive breast cancer
- Dr dang on neratinib in patients with her2 breast cancer
- Clinical trials
- Mechanism of action
- Biological Activity of Neratinib
- References
It is in development for the treatment of early- and late-stage HER2-positive breast cancer.
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.
Dr dang on neratinib in patients with her2 breast cancer
Clinical trials
Neratanib is being developed by Puma Biotechnology. It will be included in the forthcoming I-SPY2 breast cancer trial.
Mechanism of action
Neratinib inhibits the epidermal growth factor receptor by covalently binding with a cysteine side chain in that protein.
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.