Sorafenib

Sorafenib is a multi-kinase inhibitor that inhibits Raf-1 and B-RAF (IC50s = 6 and 22 µM, respectively), as well as the receptor tyrosine kinases VEGFR2, VEGFR3, PDGFRbeta, FLT3, and c-Kit (IC50s = 90, 15, 20, 57, and 58 nM, respectively). It is selective for these kinases over 12 other kinases, including ERK1, MEK1, EGFR, and HER2 (IC50s = >10 µM for all). Sorafenib inhibits proliferation of PLC/PRF/5 and HepG2 cells (IC50s = 6.3 and 4.5 µM, respectively) and induces apoptosis in these cells. It completely inhibits tumor growth in a PLC/PRF/5 mouse xenograft model when administered at a dose of 30 mg/kg and reduces basic FGF-induced angiogenesis in a Matrigel(TM) assay in vivo. Sorafenib (10 µM) induces ferroptotic cell death in HT-1080 fibrosarcoma cells, an effect that can be blocked by the ferroptosis inhibitors ferrostatin-1 (Cay-17729), deferoxamine (Cay-14595), and beta-mercaptoethanol, but does not induce ferroptosis in a variety of other cancer cell lines. It inhibits glutamate release by the system xc- cystine/glutamate transporter in HT-1080 cells when used at concentrations ranging from 2.5 to 10 µM, decreases glutathione levels, and increases lipid peroxidation. Sorafenib also inhibits replication of hepatitis C virus (HCV) in Huh7.5 cells (IC50 = 7.2 µM). Formulations containing sorafenib have been used in the treatment of hepatocellular, renal cell, and thyroid carcinomas.Formal Name: 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-2-pyridinecarboxamide. CAS Number: 284461-73-0. Synonyms: BAY 43-9006. Molecular Formula: C21H16ClF3N4O3. Formula Weight: 464.8. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMSO: 20 mg/ml, DMSO:PBS(pH 7.2) (1:2): 0.3 mg/ml. lambdamax: 204, 266 nm. SMILES: O=C(NC)C1=NC=CC(OC2=CC=C(NC(NC3=CC(C(F)(F)F)=C(Cl)C=C3)=O)C=C2)=C1. InChi Code: InChI=1S/C21H16ClF3N4O3/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25/h2-11H,1H3,(H,26,30)(H2,28,29,31). InChi Key: MLDQJTXFUGDVEO-UHFFFAOYSA-N.