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Sorafenib Tosylate

CAS No. : 475207-59-1

MCE 国际站：Sorafenib Tosylate

产品活性：Sorafenib Tosylate(Bay 43-9006 Tosylate) 是一种有效的口服活性 Raf 抑制剂，对Raf-1 和 B-Raf 的IC50 分别为 6 nM和 20 nM。Sorafenib Tosylate 是一种多激酶抑制剂，对VEGFR2，VEGFR3，PDGFRβ，FLT3和 c-Kit 的 IC50 分别为 90 nM，15 nM，20 nM，57 nM 和58 nM。Sorafenib Tosylate 诱导细胞自噬 (autophagy) 和凋亡(apoptosis)，并具有抗肿瘤活性。Sorafenib Tosylate 也是一种ferroptosis 激动剂。

研究领域：MAPK/ERKPathway  |  ProteinTyrosine Kinase/RTK  |  Autophagy  |  Apoptosis

作用靶点：Raf  |  VEGFR  |  FLT3  |  Autophagy  |  Ferroptosis  |  Apoptosis

In Vitro: SorafenibTosylate also inhibits BRAFwt(IC50=22 nM), BRAFV599E (IC50=38 nM), VEGFR-2 (IC50=90 nM), VEGFR-3 (IC50=20 nM), PDGFR-β (IC50=57 nM), c-KIT (IC50=68 nM), and Flt3 (IC50=58 nM) in biochemical assays.Sorafenib-induced phosphorylation of c-Met, p70S6K and 4EBP1 issignificantly reduced when 10-0505 cells are co-treated withanti-human anti-HGF antibody, suggesting that treatment withSorafenib Tosylate leads to increased HGF secretion and activationof c-Met and mTOR targets.

In Vivo: SorafenibTosylate (10, 30, 50 and 100 mg/kg, orally) treatment inhibits thetumor growth of 06-0606 and 10-0505 xenografts in a dose-dependentmanner (P<0.01). The growth rate of 06-0606 and 10-0505xenografts is also significantly reduced by Sorafenib. The weightsof 06-0606 tumors in mice that are treated with Sorafenib 50 mg/kgand 100 mg/kg are approximately 13% and 5% of the controls,respectively. 50 mg dose of Sorafenib significantly inhibits tumorgrowth in mice with lines 5-1318, 26-1004 and 10-0505 (P<0.01).For 50 mg dose, the T/C ratio, where T and C are the median weight(mg) of Sorafenib- and vehicle-treated tumors at the end of thetreatment, respectively, for 06-0606, 26-1004, 5-1318, and 10-0505xenografts is 0.13, 0.10, 0.12 and 0.49, respectively. The survivalrate is 73.3 % in Diethyl nitrosamine (DENA) group and 83.3 % inSorafenib group compared to 100 % in the normal control group. DENAgroup shows a significant increase in liver index (1.51-foldincrease, p<0.05) compared to normal control group, whiletreatment with Sorafenib shows significant decrease (p<0.05) inliver index when compared to DENA group. The liver index inSorafenib group significantly decreases to lower than its value inthe normal control.

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