VEGFR3 (IC50 = 20 nM); Braf (IC50 = 22 nM); Raf-1 (IC50 = 6 nM); VEGFR2 (IC50 = 90 nM); PDGFRβ (IC50 = 57 nM); BrafV599E (IC50 = 38 nM); c-Kit (IC50 = 68 nM); Flt3 (IC50 = 58 nM)

甲苯磺酸索拉非尼还抑制 BRAFwt (IC50=22 nM)、BRAFV599E (IC50=38 nM)、VEGFR-2 (IC50=90 nM)、VEGFR-3 (IC50=20 nM)、PDGFR-β (IC50=57 nM)、生化检测中的 c-KIT (IC50=68 nM) 和 Flt3 (IC50=58 nM)[1]。当抗人抗 HGF 抗体同时给予 10-0505 细胞时，甲苯磺酸索拉非尼诱导的 c-Met、p70S6K 和 4EBP1 磷酸化显着降低，表明甲苯磺酸索拉非尼治疗可增加 HGF 分泌并激活 c-Met 和 mTOR 靶标。 2]。

甲苯磺酸索拉非尼（10、30、50和100 mg/kg，口服）治疗以剂量依赖性方式抑制06-0606和10-0505异种移植物的肿瘤生长（P<0.01）。索拉非尼还显着减慢异种移植物06-0606和10-0505的生长。接受索拉非尼 50 mg/kg 和 100 mg/kg 治疗的小鼠的 06-0606 肿瘤重量分别约为对照组的 13% 和 5%。索拉非尼 50 mg 剂量显着降低 5-1318、26-1004 和 10-0505 系小鼠的肿瘤生长（P<0.01）。对于 50 mg 剂量，06-0606、26-1004、5-1318 和 10-0505 异种移植物的 T/C 比率分别为 0.13、0.10、0.12 和 0.49，其中 T 和 C 是中位重量(mg) 治疗结束时经索拉非尼和媒介物治疗的肿瘤[2]。与正常对照组的100%相比，二乙基亚硝胺（DENA）组的存活率为73.3%，索拉非尼组的存活率为83.3%。与 DENA 组相比，索拉非尼治疗导致肝脏指数显着降低 (p<0.05)，但与正常组相比，DENA 组的肝脏指数显着增加（增加 1.51 倍，p<0.05）控制组。与正常对照组相比，索拉非尼组的肝脏指数显着下降至较低值[3]。

检测缓冲液含有 20 mM Tris (pH 8.2)、100 mM NaCl、5 mM MgCl2 和 0.15% β-巯基乙醇，用于组合 Raf-1 (80 ng)、wt BRAF (80 ng) 或 V599E BRAF (80 ng) 与 MEK-1 (1 μg) 一起测试化合物对不同 RAF 激酶亚型的抑制作用。将 25 μL 10 μM γ-[33P]ATP (400 Ci/mol) 添加到 RAF 激酶测定的 50 μL 终体积中，在 32°C 下孵育 25 分钟。通过过滤到磷酸纤维素垫上，获得磷酸化的MEK-1。然后使用 1% 磷酸去除未结合的放射性。利用 β 板计数器，通过微波加热干燥后测量过滤器结合的放射性[1]。

将10-0505、06-0606和26-1004肿瘤切碎并在改良Eagle培养基(MEM)中彻底清洗3次。 800×g 离心 10 分钟收集细胞。在存在或不存在 5 μg/mL 抗人肝细胞生长因子 (HGF) 抗体的情况下，用无血清 MEM 中的 3 或 6 μM 索拉非尼处理细胞 48 小时。收集并浓缩来自用索拉非尼或载体（不含抗人抗体）处理的动物的 2 mL 条件培养基后，使用蛋白质印迹法测定条件培养基中分泌的 HGF 量[2]。

Mice: Four doses of sorafenib (10, 30, 50, and 100 mg/kg daily) are given orally to mice with the 06-0606 and 10-0505 xenografts for a dose-response experiment. The number of mice in each treatment group was five. Mice with tumors are given sorafenib 50 mg/kg orally once a day for 12 days in order to study the antitumor effects of the drug. Each experiment is repeated at least twice, and there are 14 animals in each treatment group. Seven days after the tumor was implanted, treatment began. The HCC xenografts had grown to a size of about 100 mm3 by this point. Mice with tumors (14 per group) are given 200 μL of vehicle, 50 mg/kg of Sorafenib, 1 mg/kg of Rapamycin, or Rapamycin plus Sorafenib orally once daily for the specified days in order to study the effects of Rapamycin plus Sorafenib on the growth of 10-0505 xenograft. Vernier caliper measurements of the tumor's length and width are used to track tumor growth at least twice per week. The formula for calculating tumor volume is [length×width2×π/6]. The mice are killed at the conclusion of the experiment, their body weights and tumor weights are noted, and the tumors are collected for examination. Rats: Male albino rats weighing 100–120 g are used in the experiment. Following the acclimatization period, rats are weighed and divided into three groups at random: For eight weeks, the vehicle is given daily to Group 1 (a normal control group; n = 10). 200 mg/kg of DENA is administered intravenously to Group 2 (the DENA group; n=15). Group 3 (Sorafenib group; n=12) receives Sorafenib orally twice daily for two weeks following DENA intravenously. Rats are weighed, put to sleep with ether, killed after the experiment (8 weeks), and then their livers are dissected. Two rounds of ice-cold saline washing and drying are performed on fresh liver before weighing. The formula for calculating liver index is liver weight (g)/final body weight (g) x 100. Five portions of the liver are removed, one of which is preserved in 10% formalin for histopathological analysis while the other four are immediately frozen in liquid nitrogen and kept at 80°C.

[1]. 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]. Sorafenib and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma. J Cell Mol Med. 2009 Aug;13(8B):2673-83.

[3]. Sorafenib effect on liver neoplastic changes in rats: more than a kinase inhibitor. Clin Exp Med. 2016 Apr 16.

[4]. Combination of sorafenib and Valproic acid synergistically induces cell apoptosis and inhibits hepatocellular carcinoma growth via down-regulating Notch3 and pAkt. Am J Cancer Res. 2017 Dec 1;7(12):2503-2514.

C21H16CLF3N4O3.C7H8O3S

637.03

637.020

C, 52.79; H, 3.80; Cl, 5.56; F, 8.95; N, 8.80; O, 15.07; S, 5.03

475207-59-1

Sorafenib;284461-73-0

white solid powder

CC1=CC=C(C=C1)S(=O)(=O)O.CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F

IVDHYUQIDRJSTI-UHFFFAOYSA-N

InChI=1S/C21H16ClF3N4O3.C7H8O3S/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25;1-6-2-4-7(5-3-6)11(8,9)10/h2-11H,1H3,(H,26,30)(H2,28,29,31);2-5H,1H3,(H,8,9,10)

4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide;4-methylbenzenesulfonic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 2.08 mg/mL (3.27 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (3.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (3.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 2% Cremophor EL, 2% N,N-dimethylacetamide: 30 mg/mL

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Solubility in Formulation 5: 5 mg/mL (7.85 mM) in 20% HP-β-CD in Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。