S49076

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。

S49076  纯度: 99.71%

S49076是新颖高效的MET, AXL/MERFGFR1/2/3抑制剂, IC50值小于20 nM。

S49076

S49076 Chemical Structure

CAS No. : 1265965-22-7

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 ¥916 In-stock
2 mg ¥600 In-stock
5 mg ¥950 In-stock
10 mg ¥1200 In-stock
50 mg ¥3900 In-stock
100 mg ¥7100 In-stock
200 mg   询价  
500 mg   询价  

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生物活性

S49076 is a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3 with IC50 values below 20 nM.

IC50 & Target[1]

METD1246N

8 nM (IC50)

METY1248C

16 nM (IC50)

METD1246H

11 nM (IC50)

METY1248D

17 nM (IC50)

METY1248H

1 nM (IC50)

METM1268T

1 nM (IC50)

MET

1 nM (IC50)

FGFR1

18 nM (IC50)

FGFR1V561M

23 nM (IC50)

FGFR2

17 nM (IC50)

FGFR2N549H

19 nM (IC50)

FGFR3

15 nM (IC50)

AXL

7 nM (IC50)

MER

2 nM (IC50)

体外研究
(In Vitro)

S49076 potently blocks cellular phosphorylation of MET, AXL, and FGFRs and inhibits downstream signaling. S49076 inhibits the proliferation of MET- and FGFR2-dependent gastric cancer cells, blocks MET-driven migration of lung carcinoma cells, and inhibits colony formation of hepatocarcinoma cells expressing FGFR1/2 and AXL. Total inhibition of MET phosphorylation is seen after 2 hours of incubation with 10 nM S49076 and an with an IC50 of 2 nM. S49076 inhibits MET phosphorylation on this site in GTL-16 gastric carcinoma cells with an IC50 value of 3 nM. The IC50 for AXL inhibition by S49076 is 56 nM. S49076 inhibits AXL signaling via AKT with an IC50 of 33 nM[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)

In tumor xenograft models, a good pharmacokinetic/pharmacodynamic relationship for MET and FGFR2 inhibition following oral administration of S49076 is established and correlated well with impact on tumor growth. MET, AXL, and the FGFRs have all been implicated in resistance to VEGF/VEGFR inhibitors such as bevacizumab. Combination of S49076 with bevacizumab in colon carcinoma xenograft models leads to near total inhibition of tumor growth. S49076 alone caused tumor growth arrest in bevacizumab-resistant tumors[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.

分子量

438.50

Formula

C22H22N4O4S

CAS 号

1265965-22-7

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 : ≥ 31 mg/mL (70.70 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 2.2805 mL 11.4025 mL 22.8050 mL
5 mM 0.4561 mL 2.2805 mL 4.5610 mL
10 mM 0.2281 mL 1.1403 mL 2.2805 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: ≥ 2.5 mg/mL (5.70 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.70 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 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: ≥ 2.5 mg/mL (5.70 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.70 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 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
*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]. Burbridge MF, et al. S49076 is a novel kinase inhibitor of MET, AXL, and FGFR with strong preclinical activity alone and in association with bevacizumab. Mol Cancer Ther. 2013 Sep;12(9):1749-62.

Cell Assay
[1]

For GTL-16 and SNU-16 viability assays, cells are seeded in 96-well microplates at the appropriate density in media containing 10% FCS and supplemented 48 hours later with serial dilutions of S49076 in a final volume of 150 μL per well. After 96 hours (GTL-16) or 120 hours (SNU-16) incubation (corresponding to 4 doubling times), 15 μL of a solution of 5 mg/mL MTT is added to each well and the plates are incubated for 4 hours at 37°C. The formazan metabolite is solubilized in SDS for SNU-16 and, following removal of the MTT solution, in DMSO for GTL-16. Global cell viability is estimated by measurement of optical density at 540 nm[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]

Mice: Female balb/c and swiss nu/nu mice are used in the study. The hydrochloride salt of S49076 is administered orally to mice in 1% (w/v) hydroxyethylcellulose in ammonium acetate buffer pH 4.5 in a volume of 200 μL per 20 g body weight. The maximal tolerated dose of S49076 in these mice is determined to be 100 mg/kg/d (5 days a week for at least 3 weeks). Bevacizumab is dissolved in PBS and administered intraperitoneally in a volume of 200 μL per 20 g body weight[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.

参考文献
  • [1]. Burbridge MF, et al. S49076 is a novel kinase inhibitor of MET, AXL, and FGFR with strong preclinical activity alone and in association with bevacizumab. Mol Cancer Ther. 2013 Sep;12(9):1749-62.

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