Nilotinib
Nilotinib is a second-generation phenylamino pyridine tyrosine kinase inhibitor that is clinically used to treat Bcr-Abl-positive chronic myelogenous leukemia (CML). Nilotinib is an ATP-competitive inhibitor of Abl, c-Kit, and PDGFR that exhibits anticancer chemotherapeutic, anti-fibrotic, anti-allergic, and anti-inflammatory activities. In cellular and animal models of hepatocellular carcinoma, nilotinib increases activation of AMPK and inhibits protein phosphatase 2A (PP2A), inducing autophagy in vitro and inhibiting tumor xenografts growth in vivo. In hepatic stellate cells, nilotinib decreases expression of histone deacetylases 1, 2, and 4 (HDAC1/2/4), increasing apoptotic cell death. In animal models of allergic reaction and inflammation, nilotinib inhibits expression of TNF-α and prevents mast cell histamine release, decreasing paw edema and preventing systemic anaphylaxis.
References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/1894890
| Cas No. |
641571-10-0 |
|---|---|
| Purity |
≥98% |
| Formula |
C28H22F3N7O |
| Formula Wt. |
529.52 |
| Chemical Name |
4-Methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide |
| IUPAC Name |
4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide |
| Synonym |
AMN 107, Tasigna |
| Appearance |
Yellowish to off white powder |
Shaker ME, Ghani A, Shiha GE, et al. Nilotinib induces apoptosis and autophagic cell death of activated hepatic stellate cells via inhibition of histone deacetylases. Biochim Biophys Acta. 2013 Aug;1833(8):1992-2003. PMID: 23499874.
Yu HC, Lin CS, Tai WT, et al. Nilotinib induces autophagy in hepatocellular carcinoma through AMPK activation. J Biol Chem. 2013 Jun 21;288(25):18249-59. PMID: 23677989.
El-Agamy DS. Anti-allergic effects of nilotinib on mast cell-mediated anaphylaxis like reactions. Eur J Pharmacol. 2012 Apr 5;680(1-3):115-21. PMID: 22329898.
Fabbro D, Manley PW, Jahnke W, et al. Inhibitors of the Abl kinase directed at either the ATP- or myristate-binding site. Biochim Biophys Acta. 2010 Mar;1804(3):454-62. PMID: 20152788.
Quintás-Cardama A, Cortes J. Nilotinib: a phenylamino-pyrimidine derivative with activity against BCR-ABL, KIT and PDGFR kinases. Future Oncol. 2008 Oct;4(5):611-21. PMID: 18922118.
