Raf kinases and tyrosine kinases inhibitor
CAS：475207-59-1
分子式：C21H16ClF3N4O3.C7H8O3S
分子量：637.03
纯度：98%
存储：Store at -20°C

Background:

Sorafenib tosylate, also named nexavar, is a small-molecule anticancer compound [1]. It is also a novel oral Raf kinase and a vascular endothelial growth factor receptor (VEGFR) inhibitor. It inhibits tumor cell proliferation and tumor angiogenesis [2]. To HepG2 cells (1× 106), the IC50 of sorafenib tosylate is 2.09μg/ml [3].  
Raf is a mitogen-stimulated protein kinase that functions as a component of the signaling cascade that leads to the stimulation of mitogen-activated protein kinase [4].
Vascular endothelial growth factor (VEGF) is a highly specific mitogen for vascular endothelial cells [5].
Treatment with nexavar potently inhibited the cell proliferation of MV4-11 cells (FLT3-ITD) in a dose-dependent manner with an IC50 of 0.88 nM. In MV4-11 cells, sorafenib tosylate of a concentration of 100 nM induced 43.6±5.2% of the cells to undergo apoptosis whereas in EOL-1 cells a concentration as low as 10 nM induced 89.29±1.8% of the cells to be apoptotic [6].
Nude rats at the age of 6 weeks injected with 105 MDA-MB-231 cells were involved. After monotherapy with sorafenib tosylate a significant reduction of the osteolytic lesion volume was observed on days 45 and 55 and of the soft tissue component volume on day 55 in comparison to untreated animals (p < 0.05). Compared to controls, treatment with sorafenib tosylate made bone metastases show significantly decreased values of Amplitude A and kep from day 35 to 55 (Amplitude A: p<0.01; kep p<0.01 on days 35 and 55; p<0.05 on day 45) [7].
参考文献:
[1]. Chetan Lathia, John Lettieri, Frank Cihon, et al. Lack of effect of ketoconazole-mediated CYP3A inhibition on sorafenib clinical pharmacokinetics. Cancer Chemother Pharmacol, 2006, 57: 685-692.
[2]. M. J. Gnoth, S. Sandmann, K. Engel, et al. In Vitro to In Vivo Comparison of the Substrate Characteristics of Sorafenib Tosylate toward P-Glycoprotein. Drug Metabolism & Disposition, 2010, 38: 1341–1346.
[3]. Sayantan Dey, Subhadeep Roy, Nilanjana Deb, et al. Anti-carcinogenic Activity of Ruellia Tuberosa L. (Acanthaceae) Leaf Extract on Hepatoma Cell Line & Increased Superoxide Dismutase Activity on Macrophage Cell Lysate. Int J Pharm Pharm Sci, 2010, 5(Suppl 3): 854-861.
[4]. Markus Wartmann and Roger J. Davis. The Native Structure of the Activated Raf Protein Kinase Is a Membrane-bound Multi-subunit Complex. The Journal of Biological Chemistry, 1994, 269(9): 6695-6701.
[5]. Gera Neufeld, Tzafra Cohen, Stela Gengrinovitch, et al. Vascular endothelial growth factor (VEGF) and its receptors. The FASEB Journal, 1999, 13: 9-22.
[6]. D Auclair, D Miller, V Yatsula, et al. Antitumor activity of sorafenib in FLT3-driven leukemic cells. Leukemia, 2007, 21:439-445.
[7]. Maximilian Merz, Dorde Komljenovic, Stefan Zwick, et al. Sorafenib tosylate and paclitaxel induce anti-angiogenic, anti-tumour and anti-resorptive effects in experimental breast cancer bone metastases. European Journal of Cancer, 2011, 47:277-286.