Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Sorafenib (Bay 43-9006) 是一种多激酶抑制剂,抑制 Raf-1、B-Raf、VEGFR2、VEGFR3、VEGFR4、PDGFRβ、FLT3、c-Kit 等 (IC50=6/22/90/15/20/20/57/58 nM),具有口服活性。Sorafenib 具有抗肿瘤活性,可以诱导细胞自噬和凋亡,也可以激动铁死亡。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
10 mg | ¥ 329 | 现货 | ||
50 mg | ¥ 535 | 现货 | ||
100 mg | ¥ 697 | 现货 | ||
500 mg | ¥ 995 | 现货 | ||
1 g | ¥ 1,460 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 272 | 现货 |
产品描述 | Sorafenib (Bay 43-9006) is a multikinase inhibitor that inhibits Raf-1, B-Raf, VEGFR2, VEGFR3, VEGFR4, PDGFRβ, FLT3, c-Kit, and others (IC50=6/22/90/15/20/20/57/58 nM) with oral activity. Sorafenib has antitumor activity and can induce autophagy and apoptosis as well as agonistic iron death. |
靶点活性 | c-Kit:68 nM (cell free), PDGFRβ:57 nM (cell free), Braf V599E:38 nM (cell free), Raf-1:6 nM (cell free0, B-Raf:22 nM (cell free), VEGFR3:20 nM (cell free) |
体外活性 |
方法:人肝癌细胞 HepG2 和 HuH-7 用 Sorafenib (2-20 µmol/L) 处理 48 h,使用 MTT 方法检测细胞生长抑制情况。 结果:Sorafenib 剂量依赖性地抑制 HepG2 和 HuH-7 细胞生长,IC50 均约为 6 µmol/L。[1] 方法:人急性早幼粒白血病细胞 NB4 用 Sorafenib (1.5-12 µM) 处理 24-48 h,使用 Flow Cytometry 方法检测细胞凋亡情况。 结果:Sorafenib 剂量依赖性 NB4 细胞凋亡,早期和晚期凋亡细胞比例均显著增加。[2] 方法:大鼠肝胆管癌细胞 LCC-2 用 Sorafenib (2.5-5 μM) 处理 12 h,使用 JC-1 染料检测线粒体膜电位。 结果:Sorafenib 使分离的线粒体去极化。[3] |
体内活性 |
方法:为检测体内抗肿瘤活性,将 Sorafenib (7.5-60 mg/kg) 口服给药给携带人肿瘤 MDA-MB-231、Colo-205、HT-29、DLD-1、NCI-H460 和 A549 的 NCr-nu/nu 小鼠,每天一次,持续二至四天。 结果:Sorafenib 在各种人类肿瘤异种移植物模型中显示出广泛的口服抗肿瘤功效。[4] 方法:为检测体内抗肿瘤活性,将 Sorafenib (30 mg/kg/每周五次) 和 everolimus (10 mg/kg/每周三次) 灌胃给药给携带去势抵抗性前列腺癌肿瘤 CRPC 的 PTEN 突变小鼠,每天一次,持续四周。 结果:Sorafenib 给药增加了 CRPC 中雄激素受体 p-GSK3β 和 p-ERK1/2 的表达水平。Sorafenib 和 everolimus 联合治疗克服了 CRPC 单药的治疗逃逸。[5] |
激酶实验 | Recombinant baculoviruses expressing Raf-1 (residues 305–648) and B-Raf (residues 409–765) are purified as fusion proteins. Full-length human MEK-1 is generated by PCR and purified as a fusion protein from Escherichia coli lysates. Sorafenib tosylate is added to a mixture of Raf-1 (80 ng), or B-Raf (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. Human VEGFR2 (KDR) kinase domain is expressed and purified from Sf9 lysates. Time-resolved fluorescence energy transfer assays for VEGFR2 are performed in 96-well opaque plates in the time-resolved fluorescence energy transfer format. Final reaction conditions are as follows: 1 to 10 μM ATP, 25 nM poly GT-biotin, 2 nM Europium-labeled phospho (p)-Tyr antibody (PY20), 10 nM APC, 1 to 7 nM cytoplasmic kinase domain in final concentrations of 1% DMSO, 50 mM HEPES (pH 7.5), 10 mM MgCl2, 0.1 mM EDTA, 0.015% Brij-35, 0.1 mg/mL BSA, and 0.1% β-mercaptoethanol. Reaction volumes are 100 μL and are initiated by the addition of enzyme. Plates are read at both 615 and 665 nM on a Perkin-Elmer VictorV Multilabel counter at ~1.5 to 2.0 hours after reaction initiation. Signal is calculated as a ratio: (665 nm/615 nM) × 10,000 for each well. For IC50 generation, Sorafenib tosylate is added before the enzyme initiation. A 50-fold stock plate is made with Sorafenib tosylate serially diluted 1:3 in a 50% DMSO/50% distilled water solution. Final Sorafenib tosylate concentrations range from 10 μM to 4.56 nM in 1% DMSO. |
细胞实验 | Tumor cell lines were plated at 2 × 105 cells per well in 12-well tissue culture plates in DMEM growth media (10% heat-inactivated FCS) overnight. Cells were 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 in 0.1% DMSO for 120 minutes to measure changes in basal pMEK 1/2, pERK 1/2, or pPKB. Cells were washed with cold PBS (PBS containing 0.1 mmol/L vanadate) and lysed in a 1% (v/v) Triton X-100 solution containing protease inhibitors. Lysates were 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 were developed with horseradish peroxidase (HRP)-conjugated secondary antibodies and developed with Amersham ECL reagent on Amersham Hyperfilm [1]. |
动物实验 | Female NCr-nu/nu mice (Taconic Farms, Germantown, NY) were used for all studies. Three to five million cells were injected s.c. into the right flank of each mouse. DLD-1 tumors were established and maintained as a serial in vivo passage of s.c. fragments (3 × 3 mm) implanted in the flank using a 12-gauge trocar. A new generation of the passage was initiated every three weeks, and studies were conducted between generations 3 and 12 of this line. Treatment was initiated when tumors in all mice in each experiment ranged in size from 75 to 144 mg for antitumor efficacy studies and from 100 to 250 mg for studies of microvessel density and ERK phosphorylation. All treatment was administered orally once daily for the duration indicated in each experiment. |
别名 | 索拉非尼, Bay 43-9006 |
化合物与蛋白结合的复合物 |
P38 in complex with Sorafenib |
分子量 | 464.82 |
分子式 | C21H16ClF3N4O3 |
CAS No. | 284461-73-0 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
H2O: < 1 mg/mL (insoluble or slightly soluble)
DMF: 3.33mg/ml(7.17mM)
DMSO: 59 mg/mL (126.9 mM)
Ethanol: < 1 mg/mL (insoluble or slightly soluble)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMF / DMSO | 1 mM | 2.1514 mL | 10.7569 mL | 21.5137 mL | 53.7843 mL |
5 mM | 0.4303 mL | 2.1514 mL | 4.3027 mL | 10.7569 mL | |
DMSO | 10 mM | 0.2151 mL | 1.0757 mL | 2.1514 mL | 5.3784 mL |
20 mM | 0.1076 mL | 0.5378 mL | 1.0757 mL | 2.6892 mL | |
50 mM | 0.043 mL | 0.2151 mL | 0.4303 mL | 1.0757 mL | |
100 mM | 0.0215 mL | 0.1076 mL | 0.2151 mL | 0.5378 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
Sorafenib 284461-73-0 Angiogenesis Apoptosis Autophagy MAPK Tyrosine Kinase/Adaptors Raf VEGFR FLT Ferroptosis PDGFR c-Kit inhibit Inhibitor CD135 Vascular endothelial growth factor receptor 索拉非尼 Fms like tyrosine kinase 3 Raf kinases Bay 43-9006 Cluster of differentiation antigen 135 FLT3 inhibitor