| CAS |
No.284461-73-0 |
| 中文名称 |
索拉非尼(10mM in DMSO,无菌） |
| 英文名称 |
Sorafenib(10mM in DMSO，Sterile） |
| 分子式 |
C21H16ClF3N4O3 |
| 分子量 |
464.83 |
| 溶解性 |
请根据自己的实验要求使用。 |
| 外观(性状) |
无菌溶液 |
| 储存条件 |
Stroe at -20℃，6 months. |
| 靶点 |
Ferroptosis;Raf |
| 通路 |
Apoptosis;MAPK |
| 背景说明 |
是一种有效的Raf 抑制剂，也是一种多激酶抑制剂，对VEGFR2，VEGFR3，PDGFRβ，FLT3和c-Kit均有抑制效果。还可以诱导细胞自噬 (autophagy) 和凋亡 (apoptosis)，也是一种 ferroptosis 激动剂。 |
| 生物活性 |
Sorafenib (Bay 43-9006) is a potent and orally active Raf inhibitor with IC50s of 6 nM and 20 nM for Raf-1 and B-Raf， respectively. Sorafenib is a multikinase inhibitor with IC50s of 90 nM， 15 nM， 20 nM， 57 nM and 58 nM for VEGFR2， VEGFR3， PDGFRβ， FLT3 and c-Kit， respectively. Sorafenib induces autophagy and apoptosis. Sorafenib has anti-tumor activity. Sorafenib is a ferroptosis activator.[1-4] |
| In Vitro |
Sorafenib (BAY 43-9006) 在生化分析中，还抑制 BRAFwt (IC50=22 nM)，BRAFV599E (IC50=38 nM)，VEGFR-2 (IC50=90 nM)，VEGFR-3 (IC50=20 nM)，PDGFR-β (IC=20 nM) >50=57 nM)、c-KIT (IC50=68 nM) 和 Flt3 (IC50=58 nM)。在 MDA-MB-231 乳腺癌细胞中，Sorafenib 完全阻断 MAPK 通路的激活。细胞与 Sorafenib (0.01 至 3 μM) 预孵育，并以剂量依赖性方式抑制基础 MEK 1/2 和 ERK 1/2 磷酸化 (IC50，分别为 40 和 100 nM)[1]。 |
| In Vivo |
Sorafenib 在一组人类肿瘤异种移植模型中表现出广泛的口服抗肿瘤功效。Sorafenib 以 7.5 至 60 mg/kg 的剂量口服给药。与相应的对照组相比，任何处理组都没有致死率，体重减轻也没有增加。在六种模型中的五种模型中，每日口服 Sorafenib (30 至 60 mg/kg) 可在处理期间产生完全的肿瘤停滞[1]。二乙基亚硝胺 (DENA) 组的存活率为 73.3%，Sorafenib 组为 83.3%，而正常对照组为 100%。与正常对照组相比，DENA 组肝脏指数显著增加 (增加 1.51 倍，p[2]。 |
| 细胞实验 |
The MDA-MB-231 human mammary adenocarcinoma cell lines are plated at 2×105 cells per well in 12-well tissue culture plates in DMEM growth media (10% heat-inactivated FCS) overnight. Cells are washed once with serum-free media and incubated in DMEM supplemented with 0.1% fatty acid-free BSA containing various concentrations of BAY 43-9006 (0.01， 0.03 ， 0.1， 0.3， 1， 3 μM) in 0.1% DMSO for 120 minutes to measure changes in basal pMEK 1/2， pERK 1/2， or pPKB. Cells are washed with cold PBS (PBS containing 0.1 mM vanadate) and lysed in a 1% (v/v) Triton X-100 solution containing protease inhibitors. Lysates are clarified by centrifugation， subjected to SDS-PAGE， transferred to nitrocellulose membranes， blocked in TBS-BSA， and probed with anti-pMEK 1/2 (Ser217/Ser221; 1:1000)， anti-MEK 1/2， anti-pERK 1/2 (Thr202/Tyr204; 1:1000)， anti-ERK 1/2， anti-pPKB (Ser473; 1:1000)， or anti-PKB primary antibodies. Blots are developed with horseradish peroxidase (HRP)-conjugated secondary antibodies and developed with Amersham ECL reagent on Amersham Hyperfilm[1]. |
| 动物实验 |
Mice[1] Female NCr-nu/nu mice are used. Mice bearing 75 to 150 mg tumors are treated orally with Sorafenib (7.5 to 60 mg/kg)， administered daily for 9 days. In each model， Sorafenib produces dose-dependent tumor growth inhibition with no evidence of toxicity， as measured by increased weight loss relative to control animals or drug-related lethality. In parallel to the antitumor efficacy studies， additional groups of four mice bearing 100 to 200 mg tumors are treated orally with vehicle or Sorafenib (30 to 60 mg/kg)， administered daily for 5 days， which is the shortest treatment duration producing complete tumor stasis in the treated groups. Rats[2] In the study， 100- to 120-g male albino rats are utilized. After acclimatization period， rats are weighed and randomly divided into three groups: Group 1 (normal control group; n=10) is given the vehicle daily for 8 weeks. Group 2 (DENA group; n=15) receive i.p. single dose of 200 mg/kg DENA. Group 3 (Sorafenib group; n=12) is given Sorafenib orally at a dose of 10 mg/kg daily for 2 weeks， 6 weeks after DENA i.p. injection. At the end of the experiment (8 weeks)， rats are weighed， anesthetized by ether， and killed， and their livers are dissected. Fresh liver is washed twice with ice-cold saline， dried on clean paper towel， and weighed. Liver index is calculated as liver weight (g)/final body weight (g)×100. The liver is divided into five portions: one portion is preserved in 10 % formalin for histopathological examination and the other portions are immediately frozen in liquid nitrogen and stored at ?80°C. |
| 激酶实验 |
To test compound inhibition against various RAF kinase isoforms， Sorafenib is added to a mixture of Raf-1 (80 ng)， wt BRAF， or V599E BRAF (80 ng) with MEK-1 (1 μg) in assay buffer [20 mM Tris (pH 8.2)， 100 mM NaCl， 5 mM MgCl2， and 0.15% β-mercaptoethanol] at a final concentration of 1% DMSO. The RAF kinase assay (final volume of 50 μL) is initiated by adding 25 μL of 10 μM γ-[33P]ATP (400 Ci/mol) and incubated at 32°C for 25 minutes. Phosphorylated MEK-1 is harvested by filtration onto a phosphocellulose mat， and 1% phosphoric acid is used to wash away unbound radioactivity. After drying by microwave heating， a β-plate counter is used to quantify filter-bound radioactivity[1]. |
| 数据来源文献 |
[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 Oct 1;64(19):7099-109.
[2]. El-Ashmawy NE， et al. Sorafenib effect on liver neoplastic changes in rats: more than a kinase inhibitor. Clin Exp Med. 2016 Apr 16.
[3]. Jin W， et al. Long non-coding RNA TUC338 is functionally involved in sorafenib-sensitized hepatocarcinoma cells by targeting RASAL1. Oncol Rep. 2017 Jan;37(1):273-280.
[4]. Li M， et al. Activation of an AKT/FOXM1/STMN1 pathway drives resistance to tyrosine kinase inhibitors in lung cancer. Br J Cancer. 2017 Aug 29. |
| 规格 |
1ml |
| 单位 |
瓶 |
中文
英语
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