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- 2025年07月22日
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- 详细信息
- 文献和实验
- 技术资料
- 保存条件：
Powder:-20℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year
- 保质期：
Powder:-20℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year
- 英文名：
S-49076
- 库存：
现询
- 供应商：
北京索莱宝科技有限公司
- CAS号：
1265965-22-7
- 规格：
100mg/50mg/10mg/5mg/2mg
| 规格： | 100mg | 产品价格： | ￥5790.0 |
|---|---|---|---|
| 规格： | 50mg | 产品价格： | ￥3490.0 |
| 规格： | 10mg | 产品价格： | ￥1090.0 |
| 规格： | 5mg | 产品价格： | ￥690.0 |
| 规格： | 2mg | 产品价格： | ￥490.0 |
| 基本信息 | |
| CAS | No.1265965-22-7 |
| 英文名称 | S-49076 |
| 分子式 | C22H22N4O4S |
| 分子量 | 438.5 |
| 溶解性 | Soluble in DMSO ≥3mg/mL(Need ultrasonic) |
| 纯度 | ≥98% |
| 外观(性状) | Solid |
| 储存条件 | Powder:-20℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| SMILES | C1COCCN1CC2=CNC(=C2)C=C3C4=C(C=CC(=C4)CN5C(=O)CSC5=O)NC3=O |
| InChIKey | AREYWCZYVPSHGS-NVMNQCDNSA-N |
| InChI | InChI=1S/C22H22N4O4S/c27-20-13-31-22(29)26(20)12-14-1-2-19-17(8-14)18(21(28)24-19)9-16-7-15(10-23-16)11-25-3-5-30-6-4-25/h1-2，7-10，23H，3-6，11-13H2，(H，24，28)/b18-9- |
| PubChem CID | 49870909 |
| 靶点 | FGFR;c-Met/HGFR;AXL/MER |
| 通路 | Angiogenesis; Protein Tyrosine Kinase/RTK |
| 背景说明 | 是一种有效的Met (c-Met)， AXL/MER和FGFR1/2/3抑制剂。 |
| 生物活性 | S49076 is a novel， potent inhibitor of MET， AXL/MER， and FGFR1/2/3 with IC50 values below 20 nM.[1] |
| 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]. |
| 细胞实验 | 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]. |
| 细胞实验 | 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]. |
| 动物实验 | 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]. |
| 数据来源文献 | [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. |
| 单位 | 瓶 |
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