Sorafenib Inhibitor CAS No. 284461-73-0

Cat. No.	Name	Size	Price
KI0237	Sorafenib	5 mg	$160
	Sorafenib	10 mg	$200
	Sorafenib	50 mg	$640
	Sorafenib	100 mg	$1080

Chemical Characteristic

Product Name	Sorafenib
Synonyms	Nexavar, BAY 43-9006
CAS No.	284461-73-0
Molecular Weight	464.825
Formula	C₂₁H₁₆ClF₃N₄O₃
Chemical Name	4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide
Smiles	c1(cc(ccn1)Oc1ccc(cc1)NC(=O)Nc1cc(c(cc1)Cl)C(F)(F)F)C(=O)NC
Chemical Structure

Biological activities

Sorafenib is a small molecular inhibitor of several tyrosine protein kinases including VEGFR (vascular endothelial growth factor receptors) and PDGFR (platelet-derived growth factor receptors) and Raf kinases. Sorafenib prevents mouse VEGFR-2, VEGFR-3 and PDGFR-β with IC50 of 15, 20 and 57 nM, respectively. Sorafenib inhibits wild-type B-Raf and mutant B-Raf^V599E with IC50 of 22 and 38 nM, respectively. Sorafenib inhibits Raf-1 with an IC50 of 6 nM. ^[1] Sorafenib inhibits oncogenic Ret kinase activity with an IC50 of 50 nM. Sorafenib arrests the growth of NIH3T3 and RAT1 fibroblasts transformed by oncogenic Ret and of thyroid carcinoma cells that harbor spontaneous oncogenic Ret alleles. Sorafenib inhibits the growth of cells carrying Ret^V804L or Ret^V804M with IC50 of 0.11 and 0.15 µM, respectively. ^[2] Sorafenib potently inhibits FLT3-WT (wild type fms-like tyrosyl kinase-3), FLT3-ITD (internal tandem duplication) and FLT3^D835Y with IC50 of 32.6, 2.8 and 103.5 nM. The K_{i values of sorafenib for FLT3-WT, FLT3-ITD and FLT3^D835Y are 18.7, 1.5 and 44 nM, respectively. ^[3] Once daily oral dosing of sorafenib reveals broad-spectrum antitumor activity in colon, breast, and non??mall-cell lung cancer xenograft models.^[1] After 3 weeks of oral treatment with sorafenib (60 mg/kg/day), the volume of TT cell xenografts is reduced from 72.5 to 44 mm3, whereas in vehicle-treated mice, mean tumor volume increases to 408 mm3. ^[2] Sorafenib induces regression of subcutaneous FLT3-ITD tumors in athymic mice. ^[3] Sorafenib produces significant tumor growth inhibition (TGI) and a reduction in tumor vasculature of both ectopic and orthotopic Renca and 786-O tumors, at a dose as low as 15 mg/kg when administered daily.^[4]}

Protocols

Final sorafenib concentrations ranges from 10 µM to 4.56 nM in 1% DMSO.^[1]

References

[1] Wilhelm SM, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004, 64(19): 7099-7109. [2] Carlomagno F, et al. BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst. 2006, 98(5): 326-334. [3] Auclair D, et al. Antitumor activity of sorafenib in FLT3-driven leukemic cells. Leukemia. 2007, 21(3): 439-445. [4] Chang YS, et al. Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models.Cancer Chemother Pharmacol. 2007, 59(5): 561-574.

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