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Savolitinib(AZD6094,HMPL-504)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Savolitinib(AZD6094,HMPL-504)图片
CAS NO:1313725-88-0
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 345.36
Formula C17H15N9
CAS No. 1313725-88-0
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 16 mg/mL (46.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)NA
SynonymsSavolitinib; Volitinib; HMPL 504; AZD6094; HMPL504; AZD 6094; HMPL-504; AZD-6094; Orpathys; HUTCHMED
SMILES CodeCN1N=CC(C2=CN=C3C(N([C@H](C4=CN5C(C=C4)=NC=C5)C)N=N3)=N2)=C1
实验参考方法
In Vitro

In vitro activity: Savolitinib has exquisite kinase selectivity and excellent potency. It displays a high selectivity across a gastric cell line panel, potently inhibiting cell growth only in those lines with dysregulated cMET (EC50 values 0.6 nM/L-12.5 nM/L). Savolitinib has high membrane permeability without efflux transport across Caco-2 cell monolayer and exhibits negligible P-gp inhibition (IC50> 17 μM). Savolitinib shows no significant reversible or mechanism-based CYP inhibition in human liver microsomes, and no induction of CYP1A2 and CYP3A4 in human hepatocytes.


Kinase Assay: Savolitinib has IC50 values of 5 nM and 3 nM for c-Met and p-Met respectively. It exhibits high selectivity for c-Met over 274 other kinases.


Cell Assay: After incubation overnight, NCI-H441 cells are then treated with serially diluted test compounds at 37 ℃ for 1 h. Then the medium is removed, and cells are lysed in 100 μL/well lysis buffer (1% NP-40, 20 mM Tris/pH 8.0, 137 mM NaCl, 10% glycerol, 2 mM EDTA, 1 mM activated sodium orthovanadate, 10 mg/mL Aprotinin, 10 mg/mL Leupeptin). The plates containing cell lysate are kept at -80℃ overnight. The next day, the plates are thawed on ice, mixed gently. 25 μL/well of lysates are added into the assay plates pre-coated with anti-p-Met antibody to detect p-c-Met signal. p-c-Met level is determined at 450 nm and 570 nm.

In VivoSavolitinib demonstrates dose-dependent tumor growth inhibition in a U87MG subcutaneous xenograft model. Its treatment leads to pharmacodynamic modulation of c-MET signaling and potent tumor stasis in 3/3 cMET-dysregulated gastric cancer patient-derived tumor xenograft models, but has negligible activity in a gastric cancer control mode. Savolitinib has moderate plasma protein binding rate (60%~70% in rat, dog, and human; 40% in mouse; 80% in monkey) and exhibits wide distribution to different organs in rat, with high exposures in liver and kidney, very low in brain, spinal cord and testis compared to the plasma level.
Animal model Athymic mice
Formulation & Dosage Prepared in 0.5% CMC-Na (oral); 0.25% DMSO, 10% Solutol, 10% Ethanol and 79.75% Saline (i.v.); 1.0, 2.5 and 10.0 mg/kg (oral); 2.5 mg/kg (i.v.)
References Mol Oncol. 2015 Jan;9(1):323-33; J Med Chem. 2014 Sep 25;57(18):7577-89.