索凡替尼 T4075

Product Introduction
Bioactivity


英文名: Sulfatinib

描述: Sulfatinib (KDR-IN-1) (HMPL-012) 是一种有效且高度选择性的酪氨酸激酶抑制剂，可抑制VEGFR1/2/3，FGFR1和CSF1R，IC50范围为1 到 24 nM 之间。

细胞实验: A CHO cellline stably transfected with hEGR cDNA and expressing hERG channels is used for the study.Whole-cell recording are performed using a 700B. Test compound is prepared as a 10 mM DMSO stock solution in a glass vial and is diluted using External Solution, the dilution is prepared no longer than 30 minutes before use. After achieving whole-cell configuration, the cells are monitored for 90 seconds to assess stability and washed with external solution for 66 sec. External solution containing 0.1% DMSO (vehicle) is applied to the cells to establish the baseline. After allowing the current to stabilize for 3 min, the test compound is applied. The test solution is added in 4 steps and the cells are kept in the test solution until the compound is effect reached a steady state or for a maximum of 6 min. Subsequently, the positive control (10 nM cisapride) is added. Washout with external solution is performed until the recovery of the current reached a steady state[1].

激酶实验: The KDR kinase inhibition activity is tested using the the Z-lyte assay kit. Tyr1 peptide is used to test the KDR kinase inhibitory activity of N-(2-(dimethylamino)-ethyl)-1-(3-((4-((2-methyl-1H-indol-5-yl)oxy)pyrimidin-2-yl)amino)phenyl)methanesulfonamide. The testing system contains 300ng/ml of recombinant human KDR catalytic domain, 10 μM of ATP, 1 μM of substrate peptide, and a test compound at a series of different concentrations in 384-well plate; total volume is 10 μL. The enzyme inhibition proceeds at room temperature (25°C), for 1 hour at room temperature on the shaker. 5ul of stop solution is added to stop the reaction. The KDR Kinase inhibition activity of a test compound is calculated based on the method recommended by the manufacturer. The IC50 values of the KDR kinase inhibition activity are calculated using XLfit software[1].

动物实验: The phamacokinetics of the test componds are studied with male ICR mice (n=6 for each group, weight 20-30 g) after a single intraveneous and oral dosing at 2.5 and 10 mg/kg, respectively. For i.v. dosing formulation, the test compound is dissolved in DMSO (0.25%)-solutol(10%)-ethanol(10%)-physiological saline(79.75%) at the concentration of 0.25 mg/mL. And the p.o. Dosing formulation (1 mg/mL) is prepared with 0.5% CMC-Na. After i.v. Or p.o. Dosing, blood samples are collected via the ophthalmic vein at 0 (pre-close), 5, 15, 30 min and 1, 1.5, 2, 4, 8, 24 h, anti-coagulated with heparin-Na. After centrifugation, plasma samples are seprated and protein precipitated with acetonitrilel containing internal standard.\

体外活性: Sulfatinib inhibits VEGFR1, 2, and 3, FGFR1 and CSF1R kinases with IC 50 s in a range of 1 to 24 nM. Sulfatinib strongly blocks VEGF induced VEGFR2 phosphorylation in HEK293KDR cells and CSF1 stimulated CSF1R phosphorylation in RAW264.7 cells with IC 50 of 2 and 79 nM, respectively. Sulfatinib also attenuates VEGF or FGF stimulated HUVEC cells proliferation with IC 50 < 50 nM [1]. Also, it is a hERG inhibitor with IC 50 of 6.8 μM in CHO cell [2].

体内活性: A single oral dosing of Sulfatinib inhibits VEGF stimulated VEGFR2 phosphorylation in lung tissues of nude mice in an exposure-dependent manner in animal studies. Besides, elevation of FGF23 levels in plasma 24 hours post dosing suggests suppression of FGFR signaling. Sulfatinib demonstrates potent tumor growth inhibition in multiple human xenograft models and decreases CD31 expression remarkably, suggesting strong inhibition on angiogenesis through VEGFR and FGFR signaling. In a syngeneic murine colon cancer model CT-26, Sulfatinib demonstrates moderate tumor growth inhibition after single agent treatment [1]. After oral dosing of 10 mg/kg, the AUC and C max are 397 ng/mL and 138ng/mL in the mouse, respectively [1].

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 30 mg/mL


关键字: Sulfatinib

相关产品: Orantinib | Delphinidin chloride | hCA/VEGFR-2-IN-4 | Chiauranib | Takeda-6d | MAZ51 | VEGFR-3-IN-1 | Treprostinil Sodium | Vomifoliol | SU14813 maleate

相关库: JAK-STAT Compound Library | Drug Repurposing Compound Library | Anti-Cancer Drug Library | Membrane Protein-targeted Compound Library | Bioactive Compounds Library Max | Anti-Cancer Clinical Compound Library | Kinase Inhibitor Library | Inhibitor Library | Tyrosine Kinase Inhibitor Library | Anti-Cancer Active Compound Library

索凡替尼 T4075信息由TargetMol中国为您提供，如您想了解更多关于索凡替尼 T4075报价、型号、参数等信息，欢迎来电或留言咨询。

注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途