Neratinib (HKI-272) is an orally-available, quinazoline-based, irreversible inhibitor of HER-2 and EGFR kinases, with IC50 values of 59 and 92 nM, respectively. [1] Neratinib treatment in cells results in expected downstream inactiviation of signal transduction events, leading to cell cycle arrest at the G1-S-phase transition. [2] Neratninb is selective over a broad range of serine-threonine and receptor tyrosine kinases. In cell proliferation assays, Neratinib inhibits mouse fibroblast cell lines (3T3) transfected with HER-2 at and IC50 of 3 nM. Additionally, inhibition of other HER-2- or EGFR-overexpressing celll lines such as SK-Br-3, BT474, and A431 was shown to be at IC50s of 2, 2, and 81 nM, respectively. [2]
Neratinib effectively inhibits phosphorylation of BT474, MPAK, and Akt at concentrations of 5, 2, and 2 nM, respectively. Phase I trials have shown that Neratinib can achieve stable disease control for over 6 months in NSCLC that has progressed after treatment with gefitinib or erlotinib. [3]
Technical information:
| Chemical Formula: | C30H29ClN6O3 | |
| CAS #: | 698387-09-6 | |
| Molecular Weight: | 557.04 | |
| Purity: | > 98% | |
| Appearance: | White | |
| Chemical Name: | (E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-3-cyano-7-ethoxyquinolin-6-yl)-4-(dimethylamino)but-2-enamide | |
| Solubility: | Up to 5 mM in DMSO | |
| Synonyms: | HKI-272, HKI272, HKI 272, Neratinib |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
Reference:
| 1. | Wissner et al., The development of HKI-272 and related compounds for the treatment of cancer. Arch. Pharm. Chem. 2008, 341(8), 465-477. Pubmed ID: 18493974 |
| 2. | Rabindran et al., Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res. 2004, 64, 3958-3966. Pubmed ID: 15173008 |
| 3. | Wong, K-K., HKI-272 in Non-Small Cell Lung Cancer. Clin. Cancer Res. 2007, 13, 4593-4596. Pubmed ID: 17671147 |
Other Information:
Product Specification (pdf)
MSDS (pdf)
Certificate of Analysis is available upon request.
