Sorafenib(Synonyms: 索拉非尼; Bay 43-9006)

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

Sorafenib (Synonyms: 索拉非尼; Bay 43-9006) 纯度: 99.90%

Sorafenib (Bay 43-9006) 是一种有效的口服活性 Raf 抑制剂,对 Raf-1B-RafIC50 分别为 6 nM 和 20 nM。Sorafenib 是一种多激酶抑制剂,对 VEGFR2VEGFR3PDGFRβFLT3c-KitIC50 分别为 90 nM,15 nM,20 nM,57 nM 和 58 nM。Sorafenib 诱导细胞自噬 (autophagy) 和凋亡 (apoptosis),并具有抗肿瘤活性。Sorafenib 也是一种 ferroptosis 激动剂。

Sorafenib(Synonyms: 索拉非尼; Bay 43-9006)

Sorafenib Chemical Structure

CAS No. : 284461-73-0

规格 价格 是否有货 数量
Free Sample (0.1-0.5 mg)   Apply now  
10 mM * 1 mL in DMSO ¥500 In-stock
10 mg ¥450 In-stock
50 mg ¥650 In-stock
100 mg ¥850 In-stock
500 mg ¥1200 In-stock
1 g   询价  
5 g   询价  

* Please select Quantity before adding items.

Sorafenib 相关产品

相关化合物库:

  • Covalent Screening Library Plus
  • Drug Repurposing Compound Library Plus
  • FDA-Approved Drug Library Plus
  • FDA-Approved Drug Library Mini
  • Bioactive Compound Library Plus
  • Apoptosis Compound Library
  • Immunology/Inflammation Compound Library
  • Kinase Inhibitor Library
  • MAPK Compound Library
  • Protein Tyrosine Kinase Compound Library
  • FDA-Approved Drug Library
  • Anti-Cancer Compound Library
  • CNS-Penetrant Compound Library
  • Autophagy Compound Library
  • Drug Repurposing Compound Library
  • Covalent Screening Library
  • Differentiation Inducing Compound Library
  • Reprogramming Compound Library
  • Oxygen Sensing Compound Library
  • Ferroptosis Compound Library
  • Anti-COVID-19 Compound Library
  • Orally Active Compound Library
  • Glutamine Metabolism Compound Library
  • FDA Approved & Pharmacopeial Drug Library
  • Anti-Breast Cancer Compound Library
  • Anti-Lung Cancer Compound Library
  • Drug-Induced Liver Injury (DILI) Compound Library
  • Anti-Pancreatic Cancer Compound Library
  • Anti-Blood Cancer Compound Library
  • Targeted Therapy Drug Library
  • Angiogenesis Related Compound Library
  • Food-Sourced Compound Library
  • Targeted Diversity Library
  • Anti-Liver Cancer Compound Library
  • Rare Diseases Drug Library
  • Anti-Colorectal Cancer Compound Library

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].

IC50 & Target[1]

VEGFR3

20 nM (IC50)

Braf

22 nM (IC50)

Raf-1

6 nM (IC50)

VEGFR2

90 nM (IC50)

PDGFRβ

57 nM (IC50)

BrafV599E

38 nM (IC50)

c-Kit

68 nM (IC50)

Flt3

58 nM (IC50)

体外研究
(In Vitro)

Sorafenib (BAY 43-9006) also inhibits BRAFwt (IC50=22 nM), BRAFV599E (IC50=38 nM), VEGFR-2 (IC50=90 nM), VEGFR-3 (IC50=20 nM), PDGFR-β (IC50=57 nM), c-KIT (IC50=68 nM), and Flt3 (IC50=58 nM) in biochemical assays. In MDA-MB-231 breast cancer cells, Sorafenib completely blocks activation of the MAPK pathway. Cells are preincubated with Sorafenib (0.01 to 3 μM), and dose-dependent inhibition of basal MEK 1/2 and ERK 1/2 phosphorylation (IC50, 40 and 100 nM, respectively)[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

Sorafenib demonstrates broad oral antitumor efficacy in panel of human tumor xenograft models. Sorafenib is given orally at 7.5 to 60 mg/kg. There is no lethality and no increase in weight loss in any treated group relative to the corresponding control group. Daily oral administration of Sorafenib (30 to 60 mg/kg) produces complete tumor stasis during treatment in five of the six models[1]. The survival rate is 73.3 % in Diethyl nitrosamine (DENA) group and 83.3 % in Sorafenib group compared to 100 % in the normal control group. DENA group shows a significant increase in liver index (1.51-fold increase, p<0.05) compared to normal control group, while treatment with Sorafenib shows significant decrease (p<0.05) in liver index when compared to DENA group. The liver index in Sorafenib group significantly decreases to lower than its value in the normal control[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

分子量

464.83

Formula

C21H16ClF3N4O3

CAS 号

284461-73-0

中文名称

索拉非尼;索拉菲尼

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : ≥ 45 mg/mL (96.81 mM)

* “≥” means soluble, but saturation unknown.

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.1513 mL 10.7566 mL 21.5132 mL
5 mM 0.4303 mL 2.1513 mL 4.3026 mL
10 mM 0.2151 mL 1.0757 mL 2.1513 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: 2.08 mg/mL (4.47 mM); Suspended solution; Need ultrasonic

    此方案可获得 2.08 mg/mL (4.47 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。

    以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH₂O 中,得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.08 mg/mL (4.47 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (4.47 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
  • 3.

    请依序添加每种溶剂: 10% DMSO    90% corn oil

    Solubility: ≥ 2.08 mg/mL (4.47 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (4.47 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [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.

Kinase Assay
[1]

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1][2]

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.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献
  • [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.

所有产品仅用作科学研究或药证申报,我们不为任何个人用途提供产品和服务