Sorafenib

284461-73-0

C21H16ClF3N4O3

DMSO : >= 45 mg/mL (96.81 mM)

Protein Tyrosine Kinase/RTK; MAPK/ERK Pathway; Protein Tyrosine Kinase/RTK; Autophagy

Sorafenib is a potent multikinase inhibitor with IC₅₀s of 6 nM, 20 nM, and 22 nM for Raf-1, B-Raf, and VEGFR-3, respectively. IC50 & Target: IC50: 6 nM (Raf-1), 20 nM (VEGFR-3), 22 nM (BRAF), 57 nM (PDGFR-beta), 58 nM (Flt3), 68 nM (c-KIT), 90 nM (VEGFR-2)^[1] In Vitro: Sorafenib (BAY 43-9006) also inhibits BRAF^wt (IC₅₀=22 nM), BRAF^V599E (IC₅₀=38 nM), VEGFR-2 (IC₅₀=90 nM), VEGFR-3 (IC₅₀=20 nM), PDGFR-beta (IC₅₀=57 nM), c-KIT (IC₅₀=68 nM), and Flt3 (IC₅₀=58 nM) in biochemical assays. In MDA-MB-231 breast cancer cells, Sorafenib completely blocks activation of the MAPK pathway. Cells are preincubated with Sorafenib (0.01 to 3 uM), and dose-dependent inhibition of basal MEK 1/2 and ERK 1/2 phosphorylation (IC₅₀, 40 and 100 nM, respectively)^[1]. In Vivo: Sorafenib demonstrates broad oral antitumor efficacy in panel of human tumor xenograft models. Sorafenib is given orally at 7.5 to 60 mg/kg. There is no lethality and no increase in weight loss in any treated group relative to the corresponding control group. Daily oral administration of Sorafenib (30 to 60 mg/kg) produces complete tumor stasis during treatment in five of the six models^[1]. The survival rate is 73.3 % in Diethyl nitrosamine (DENA) group and 83.3 % in Sorafenib group compared to 100 % in the normal control group. DENA group shows a significant increase in liver index (1.51-fold increase, p<0.05) compared to normal control group, while treatment with Sorafenib shows significant decrease (p<0.05) in liver index when compared to DENA group. The liver index in Sorafenib group significantly decreases to lower than its value in the normal control^[2].