CST, 8705S, Sorafenib

Chemical Modulators for studying in the research area. Product Usage Information Sorafenib is supplied as a lyophilized powder. For a 10 mM stock, reconstitute the 10 mg in 1.57 ml DMSO. Working concentrations and length of treatment can vary depending on the desired effect, but it is typically used as a pretreatment at 0.1-10 µM for 0.5-2 hr prior to treating with a stimulator. It can also be used alone, with varying treatment times lasting up to 24 hr. Soluble in DMSO at 200 mg/ml; very poorly soluble in ethanol and water with maximum solubility in water ~10-20 µM. Storage Store lyophilized or in solution at -20ºC. In lyophlized form, the chemical is stable for 24 months. Once in solution, use within 3 months to prevent loss of potency. Background Sorafenib, also known as Bay 43-9006, is a novel multikinase inhibitor that targets the RAF family of serine/threonine kinases and tyrosine kinase receptors involved in tumor progression and tumor angiogenesis, including: VEGFR-2 (IC = 90 nM), VEGFR-3 (IC = 20 nM), PDGFR- (IC = 57 nM), c-KIT (IC = 68 nM), and Flt3 (IC = 58 nM) (1). Research studies have demonstrated that sorafenib induces apoptosis in several tumor cell lines through the down-regulation of the antiapoptotic protein myeloid cell leukemia-1 (Mcl-1). Down-regulation of Mcl-1 by sorafenib is associated with the release of cytochrome c from mitochondria into the cytosol and caspase activation, leading to apoptotic cell death (2). STAT3 inhibition by sorafenib has been observed in multiple cell types (3-5). Alternate Names angiogenesis; apoptosis; Bay 43-9006; c-KIT; Flt3; Mcl-1; PDGFR-; RAF; STAT3; VEGFR-2; VEGFR-3