Information Savolitinib (AZD6094) Savolitinib (Volitinib, AZD6094, HMPL-504) is a novel, potent, and selective MET inhibitor currently in clinical development in various indications, including PRCC. The IC50 values of this compound for c-Met and p-Met are 5 nM and 3 nM, respectively. It shows exquisite selectivity for c-Met over 274 kinase. Targets p-Met (Cell-free assay); c-Met (Cell-free assay) 3 nM; 5 nM In vitro Volitinib has exquisite kinase selectivity and excellent potency. Volitinib displays a highly selective profile 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). Volitinib has high membrane permeability without efflux transport across Caco-2 cell monolayer and exhibits negligible P-gp inhibition (IC50 > 17 μM). Volitinib shows no significant reversible or mechanism-based CYP inhibition in human liver microsomes, and no induction of CYP1A2 and CYP3A4 in human hepatocytes. In vivo In a mouse pharmacokinetic study (male ICR mice), the clearance of the compound is 4.28 L/(h·kg) and the half-time is 1.7 h. Despite its moderate oral bioavailability (F = 27.2%), the overall plasma exposure is much higher. Volitinib 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 model. Volitinib 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. In PK studies in mouse, rat and dog, Volitinib shows the rapid oral absorption (Tmax Cell Research(from reference) Cell lines：NCI-H441 cells Incubation Time：1 h
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Savolitinib (AZD6094)
Dangerous GoodsCAS number：1313725-88-0 molecular formula：C17H15N9
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| Chinese alias | 沃利替尼 | ||
| English alias | SCHEMBL12489208 | Z3041529961 | AZD6094, HMPL-504 | Q27254463 | Volitinib(Savolitinib) | 1-((S)-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 | AC-35267 | PYRIDINE, 4-(2-AMINOETHYL)- | Savolitinib (US | ||
| CAS number | 1313725-88-0 | molecular formula | C17H15N9 |
| molecular weight | 345.36 g/mol | Exact mass | - |
| PSA | 91.600 Ų | logp | 1.032 |
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Safety information
pictogram：
GHS08
Signal word：
Danger
Hazard Statement：
H360: 可能损害生育力或未出生的孩子 H361: 怀疑破坏生育力或未出生的孩子 H360D: 可能会伤害未出生的孩子
Statement of Preventive Measures：
P280: 戴防护手套/穿防护服/戴防护眼罩/戴防护面具。 P405: 密闭存放 P501: 将内容物/容器处理到。。。 P203: 使用前，获取、阅读并遵守所有安全说明。 P318: 如果暴露或担心，请就医。
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