生物活性

• 靶点

  B-Raf IC50:22nM

  C-Raf IC50:6nM

  VEGFR2 IC50:90nM

• 描述The RAS/RAF signaling pathway is an important mediator of tumor cell proliferation and angiogenesis. Sorafenib Tosylate, the tosylate form of Sorafenib, is a multitargeted inhibitor with IC50 values of 6nM, 22nM and 38nM for Raf-1, wt-BRAF and BRAF-V599E mutant, respectively, as well as less potent to mVEGFR2, mVEGFR3, mPDGFRβ, FLT3, c-Kit, VEGFR2 and FGFR1 with IC50 values of 15nM, 20nM, 57nM, 58nM, 68nM, 90nM and 580nM (measured by kinase assays), respectively. Sorafenib inhibited activation of the RAF/MEK/ERK pathway at concentration below 15μM, performing by suppressing p-Erk, in most of cell lines tested (like MDA-MB-231. Mia PaCa 2, HCT 116 and HT-29) independent of which mutation caused aberrant activation of the RAS/RAF pathway. Sorafenib targeted receptor tyrosine kinases and inhibited autophosphorylation of VEGFR-2 and PDGFR-β induced by VEGF165 (30ng/ml) in HUVECs/ NIH 3T3 cells and PDGF BB (10ng/ml) in HAoSMCs, respectively. Oral treatment with Sorafenib, at dose of 7.5-60mg/kg daily for 9 days, illustrated a spectrum of antitumor efficacy in a representative panel of tumor xenograft models in a dose-dependent manner, including MDA-MB-231, Colo-205, HT-29, DLD-1, NCI-H460 and A549. Sorafenib showed significant tumor angiogenesis activity, performing as daily oral administration of 30 or 60 mg/kg Sorafenib produced 50-80% inhibition of microvessel area and microvessel density compared with vehicle group in HT-29 tumors^[1].
• 作用机制Sorafenib is a multitargeted ATP-competitive inhibitor.^[1]
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  CAKI-1	-	Growth Inhibition Assay	48 h	GI50=3.2 μM	22560627
  EKVX	-	Growth Inhibition Assay	48 h	GI50=2.5 μM	22560627
  HT-29	-	Growth Inhibition Assay	48 h	GI50=2.5 μM	22560627

• 更多

• 动物研究
  剂量	Mice: 30 mg/kg, 60 mg/kg[4] (p.o.), 10 mg/kg - 100 mg/kg[2] (p.o.) Woodchucks: 2.5 mg/kg, 5 mg/kg[5] (p.o.)
  给药途径	p.o.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00126503	Chromophobe Renal Cell Carcino... more >>ma Clear Cell Renal Cell Carcinoma Papillary Renal Cell Carcinoma Recurrent Renal Cell Carcinoma Sarcomatoid Renal Cell Carcinoma Stage IV Renal Cell Cancer Collapse <<	Phase 1 Phase 2	Completed	-	United States, Massachusetts ... more >> Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02115 Dana-Farber Harvard Cancer Center Boston, Massachusetts, United States, 02115 Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215 United States, Pennsylvania University of Pennsylvania/Abramson Cancer Center Philadelphia, Pennsylvania, United States, 19104 United States, Tennessee Vanderbilt-Ingram Cancer Center Nashville, Tennessee, United States, 37232 Collapse <<
  NCT00126503	-	-	Completed	-	-
  NCT03606590	Hepatocellular Carcinoma	Phase 2	Recruiting	December 2020	Spain ... more >> Vall d'Hebron Institute of Oncology (VHIO) Recruiting Barcelona, Spain Contact: Teresa Macarulla, Dr.    +34-932748855    tmacarulla@vhio.net    Contact: Raquel García Pelaez    +34-934893000    rgarcia@vhio.net    Principal Investigator: Teresa Macarulla Mercade, Dr.          HM Hospitales - Centro Integral Oncológico Clara Campal Recruiting Madrid, Spain, 28050 Contact: Antonio Cubillo, Dr.       acubillo@hmhospitales.com    Principal Investigator: acubillo@hmhospitales.com acubillo@hmhospitales.com, Dr. Collapse <<

• 更多
• 参考文献

• [1] Wilhelm SM, Carter C, 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 Oct 1;64(19):7099-109.

  [2] Huynh H, Ngo VC, et al. Sorafenib and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma. J Cell Mol Med. 2009;13(8B):2673-83.

  [3] El-Ashmawy NE, Khedr EG, et al. Sorafenib effect on liver neoplastic changes in rats: more than a kinase inhibitor. Clin Exp Med. 2017;17(2):185-191.