Sorafenib Tosylate (Nexavar) is a novel, small molecular inhibitor of several tyrosine protein kinases (VEGFR and PDGFR) and RAF/MEK/ERK cascade inhibitor with an IC50 of 6, 22, 38 nM for Raf-1, wt BRAF and V599E mutant BRAF.
Targets
Target
Value
Cell Research
Cell Line
Type
Value
Description
References
In Vitro
Kinase Inhibition: Sorafenib Tosylate inhibits key kinases involved in tumor growth and angiogenesis. It potently inhibits RAF kinases, including wild-type B-Raf (IC50 = 22 nM) and the V599E mutant B-Raf (IC50 = 38 nM) [3]. Additionally, it effectively inhibits VEGFR-2 (Flk-1, IC50 = 15-90 nM), VEGFR-3 (IC50 = 20 nM), PDGFR-β (IC50 = 57 nM), c-Kit (IC50 = 68 nM), and Flt3 (IC50 = 58 nM) [3][4].
Proliferation Inhibition:
Sorafenib Tosylate significantly inhibits the proliferation of hepatocellular carcinoma (HCC) cells, such as PLC/PRF/5 (IC50 = 6.3 μM) and HepG2 (IC50 = 4.5 μM) [2].
It inhibits the proliferation of other cancer cells, such as HAoSMC (IC50 = 0.28 μM) and MDA-MB-231 (IC50 = 2.6 μM) [3][4].
Mechanistic Pathways:
In HCC cells, Sorafenib Tosylate significantly inhibits the RAF/MEK/ERK signaling pathway [2][4].
It reduces phosphorylation of downstream targets such as p70S6K and 4EBP1, affecting mTOR signaling [2].
Notably, it downregulates Mcl-1 expression and phosphorylation of eIF4E, promoting apoptosis in cancer cells [2][4].
Apoptosis Induction: Sorafenib Tosylate induces apoptosis in HCC cells through both MEK/ERK-dependent and -independent pathways [2].
It inhibits Flt-3 phosphorylation in HEK-293 cells (IC50 = 20 nM) [3].
Selectivity: Sorafenib Tosylate weakly inhibits FGFR-1 (IC50 = 580 nM) and is not active against ERK-1, MEK-1, EGFR, HER-2, IGFR-1, c-Met, PKB, PKA, CDK1/cyclinB, PKCα, PKCγ, or Pim-1 kinases [3][4].
References
Huynh H, et al. Sorafenib inhibits tumor growth and proliferation in HCC models by targeting the RAF/MEK/ERK and mTOR signaling pathways. (Int J Oncol. 2019 Mar;54(3):1123-1133. PMID: 30747223)
El-Ashmawy NE, et al. Sorafenib acts as a kinase inhibitor with broader effects beyond kinase activity, inhibiting liver neoplastic changes in rats. (Clin Exp Med, . 2017 May;17(2):185-191. PMID: 27085325)
Liu L, et al. Sorafenib inhibits RAF kinases and receptor tyrosine kinases, displaying a multitargeted anticancer profile. (Cancer Res. 2006 Dec 15;66(24):11851-8. PMID: 17178882)
Store lyophilized at -20ºC, keep desiccated. In lyophilized form, the chemical is stable for 36 months. In solution, store at -20ºC and use within 3 months to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.
溶解性数据
In vitro (25°C)
DMSO
114 mg/mL (178.95 mM)
Water
<1 mg/mL
Ethanol
Insoluble
In vivo
2% Cremophor EL, 2% N,N-dimethylacetamide
28 mg/mL
* <1 mg/ml means slightly soluble or insoluble. * Please note that Adooq tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
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