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Sorafenib

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Chemical Structure| 284461-73-0 同义名 : Bay 43-9006
CAS号 : 284461-73-0
货号 : A316727
分子式 : C21H16ClF3N4O3
纯度 : 99%
分子量 : 464.825
MDL号 : MFCD06411450
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 45 mg/mL(96.81 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

5%DMSO+45%PEG400+50%water 0.375 mg/mL

生物活性
靶点

  • VEGFR2

    VEGFR2, IC50:90 nM

    VEGFR2/Flk1, IC50:90 nM

  • PDGFRβ

    mPDGFRβ, IC50:57 nM

    PDGFRβ, IC50:57 nM

  • FGFR1

    FGFR1, IC50:580 nM

  • B-Raf

    B-Raf, IC50:22 nM

    B-Raf (V599E), IC50:38 nM
描述 The RAS/RAF signaling pathway is an important mediator of tumor cell proliferation and angiogenesis. 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
细胞系 浓度 检测类型 检测时间 活动说明 数据源
697 Growth Inhibition Assay IC50=7.05989 μM SANGER
A101D Growth Inhibition Assay IC50=21.3752 μM SANGER
A253 Growth Inhibition Assay IC50=34.2296 μM SANGER
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
NCT03565536 Thyroid Cancer, Anaplastic Phase 2 Recruiting October 30, 2019 China, Fujian ... 展开 >> Fujian Medical University Union Hospital Recruiting FuZhou, Fujian, China, 350001 Contact: bo wang, md    13705947900    wangbo@fjmu.edu.cn 收起 <<
NCT00984425 Solid Tumors Phase 1 Completed - Italy ... 展开 >> Istituto Clinco Humanitas Rozzano, Milano, Italy, 20089 收起 <<
NCT01259193 Hepatocellular Carcinoma Phase 2 Unknown July 2012 China, Shanghai ... 展开 >> Liver Cancer Institute Recruiting Shanghai, Shanghai, China, 200032 Contact: Zheng-Gang Ren, Ph.D    0086-021-64041990 ext 2137    ren.zhenggang@zs-hospital.sh.cn    Contact: Lan Zhang, Master    0086-021-64041990 ext 2171    zhang.lan@zs-hospital.sh.cn    Principal Investigator: Zheng-Gang Ren, Ph.D          Sub-Investigator: Jubo Zhang, PhD 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.15mL

0.43mL

0.22mL

10.76mL

2.15mL

1.08mL

21.51mL

4.30mL

2.15mL
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.

[4]Kuczynski EA, Lee CR, et al. Effects of Sorafenib Dose on Acquired Reversible Resistance and Toxicity in Hepatocellular Carcinoma. Cancer Res. 2015 Jun 15;75(12):2510-9.

[5]Iyer RV, Maguire O, et al. Dose-Dependent Sorafenib-Induced Immunosuppression Is Associated with Aberrant NFAT Activation and Expression of PD-1 in T Cells. Cancers (Basel). 2019 May 16;11(5). pii: E681.

[6]Nexavar