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SAR125844

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Chemical Structure| 1116743-46-4 同义名 : -
CAS号 : 1116743-46-4
货号 : A334110
分子式 : C25H23FN8O2S2
纯度 : 98%+
分子量 : 550.631
MDL号 : MFCD25976852
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 45 mg/mL(81.72 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The HGF/MET pathway plays an essential physiological role during embryogenesis, and a more restricted role in tissue regeneration and damage repair in healthy adults. In human cancer, the abnormal activation of the MET pathway is well documented. SAR125844 is a potent and highly selective inhibitor of the MET receptor tyrosine kinase (RTK) with IC50 values of 4.2, 0.22, 1.7, 6.5, 65 and 81 nM for wild-type MET, H1094Y, Y1235D, M1250T, L1195V and D1228H mutants, respectively. SAR125844 demonstrated a potent inhibition of MET phosphorylation with IC50 values of 1.4, 3.9 and 5.1 nM in Hs 746T, SNU-5 and MKN-45 cell lines, respectively. In a panel of 31 tumor cell lines, SAR125844 inhibited cell proliferation in all cell lines with MET gene amplification, with IC50 values in the nanomolar range (1-7 nM). SAR125844 (45 mg/kg) was able to completely inhibit MET kinase in 2 MET-amplified tumor models, with strong impact on downstream MAPK and PI3K pathways. Daily dosing in SNU-5 tumor bearing mice of SAR125844 at 45 mg/kg resulted in complete and almost complete tumor regression in 3/8 mice and 5/8 mice, respectively. SAR125844 (213 mg/kg) was able to maintain a long duration of MET inhibition up to 96h, and induce tumor regression in 2 MET-amplified gastric tumor models without any relevant impact on body weight[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.82mL

0.36mL

0.18mL

9.08mL

1.82mL

0.91mL

18.16mL

3.63mL

1.82mL
参考文献

[1]Shitara K, Kim TM, et al. Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer. Oncotarget. 2017 Jun 16.

[2]Ugolini A, Kenigsberg M, et al. Discovery and Pharmacokinetic and Pharmacological Properties of the Potent and Selective MET Kinase Inhibitor 1-{6-[6-(4-Fluorophenyl)-[1,2,4] triazolo[4,3-b] pyridazin-3-ylsulfanyl] benzothiazo l-2-yl}-3-(2-morpholin-4-ylethyl)urea (SAR125844). J Med Chem. 2016 Aug 11;59(15):7066-74.

[3]Egile C, Kenigsberg M, et al. The selective intravenous inhibitor of the MET tyrosine kinase SAR125844 inhibits tumor growth in MET-amplified cancer. Mol Cancer Ther. 2015 Feb;14(2):384-94