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Savolitinib

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Chemical Structure| 1313725-88-0 同义名 : 赛沃替尼（AZD6094） ;Volitinib;HMPL-504;HMPL0-504;AZD-6094
CAS号 : 1313725-88-0
货号 : A569590
分子式 : C17H15N9
纯度 : 98%
分子量 : 345.361
MDL号 : MFCD28359096
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 20 mg/mL(57.91 mM)，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 Savolitinib is a novel triazolopyrazine-based c-Met inhibitor with IC50 values of 5nM, 3nM and 6nM for inhibition of c-Met enzyme, HGF-mediated c-Met phosphorylation and HGF-induced proliferation assay in NCI-H441 cell line, respectively. Single oral dose of 3 mg/kg Savolitinib achieved inhibition of HGF-mediated c-Met phosphorylation by 84.7% at 6h post administration in mice. Oral dose of savolitinib at 1, 2.5 and 10mg/kg once daily for 21 days dose-dependently inhibited tumor growth in U87MG subcutaneous xenograft athymic nude mice model[1]. The MET D1228 site is important for Savolitinib, for the MET D1228V mutation could induce resistance to type I MET inhibitor like savolitinib[2].
作用机制 Savolitinib can bind to c-Met in a unique mode including wrapping around Met1211 c-Met in a“U-shaped” conformation. It also binds to the activation loop through Asp1228 and Lys1110 residues.[1][2]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.90mL

0.58mL

0.29mL

14.48mL

2.90mL

1.45mL

28.96mL

5.79mL

2.90mL
参考文献

[1]Jia H, Dai G, et al. Discovery of (S)-1-(1-(Imidazo[1,2-a]pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine (volitinib) as a highly potent and selective mesenchymal-epithelial transition factor (c-Met) inhibitor in clinical development for treatment of cancer. J Med Chem. 2014 Sep 25;57(18):7577-89.

[2]Bahcall M, Sim T, et al. Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer. Cancer Discov. 2016 Dec;6(12):1334-1341. Epub 2016 Sep 30.

[3]Gavine PR, Ren Y, et al. Volitinib, a potent and highly selective c-Met inhibitor, effectively blocks c-Met signaling and growth in c-MET amplified gastric cancer patient-derived tumor xenograft models. Mol Oncol. 2015 Jan;9(1):323-33.

[4]Henry RE, Barry ER, et al. Acquired savolitinib resistance in non-small cell lung cancer arises via multiple mechanisms that converge on MET-independent mTOR and MYC activation. Oncotarget. 2016 Sep 6;7(36):57651-57670.