Ensartinib-hydrochloride-X-396-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEEnsartinib hydrochlorideCat. No.: HY-103714ACAS No.: 2137030-98-7Synonyms: X-396 hydrochloride分式: CHClFNO分量: 634.36作靶点: ALK; c-Met/HGFR作通路: Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20

2、C 1 month溶解性数据体外实验 H2O : 5 mg/mL (7.88 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.5764 mL 7.8820 mL 15.7639 mL5 mM 0.3153 mL 1.5764 mL 3.1528 mL10 mM - - -请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Ensartinib hydrochloride (X-396 hydr

3、ochloride)种有效的双重 的 ALK/MET 抑制剂，IC50 分别 0.4 nM和 0.74 nM。IC50 & Target IC50: 1体外研究Ensartinib (X-396) is a potent and dual ALK/MET inhibitor with IC50s of EML4-ALK E13;A20 (IC50: 15 nM).1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEEnsartinib is also potent in H2228 lung cancer cells harboring EML4-

4、ALK E6a/b; A20 (IC50: 45 nM).Furthermore, X-376 is potent in SUDHL-1 lymphoma cells harboring NPM-ALK (IC50: 9 nM) 1.体内研究 Ensartinib (X-396) shows substantial bioavailability and moderate half-lives in vivo. Nude mice harboringH3122 xenografts are treated with Ensartinib at 25 mg/kg bid. Ensartinib

5、significantly delays the growth oftumors compared to vehicle alone. In the xenograft experiments, Ensartinib appears well-tolerated in vivo.Mouse weight is unaffected by Ensartinib treatment. Drug-treated mice appear healthy and do not displayany signs of compound related toxicity. To further assess

6、 potential side effects of Ensartinib, additionalsystemic toxicity and toxico-kinetic studies are performed in Sprague Dawley (SD) rats. Following 10 days ofrepeated oral administration of Ensartinib at 20, 40, 80 mg/kg in SD rats, all animals survive to studytermination. The no significant toxicity

7、 (NST) levels are determined to be 80 mg/kg for Ensartinib. At NSTlevels, Ensartinib achieves an AUC of 66 Mhr and a Cmax of 7.19 M 1.PROTOCOLCell Assay 1 For viability experiments, cells are seeded in 96-well plates at 25%-33% confluency and exposed to drugs.The human lung adenocarcinoma cell lines

8、 H3122 and H2228 are treated with Ensartinib (10, 30, 100, 300and 1000 nM). SUDHL-1 lymphoma cells are treated with Ensartinib (5, 10, 30, 100 and 300 nM). SY5Yneuroblastoma cells are treated with Ensartinib (30, 100, 300 and 1000 nM). At 72 hours post Ensartinibaddition, Cell Titer Blue Reagent is

9、added and fluorescence is measured on a Spectramaxspectrophotometer. All experimental points are set up in hextuplicate replicates and are performed at leasttwo independent times. IC50s are calculated using GraphPad Prism version 5 for Windows. The curves arefit using a nonlinear regression model wi

10、th a log (inhibitor) vs. response formula 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 Nude mice (nu/nu) are injected with H3122 cells. Once tumors reach an average volume of 450 mm3, a totalof 27 athymic mice harborin

11、g H3122 tumors are randomized and dosed via oral gavage with 25 mg/kgEnsartinib or the control vehicle. Two, five, and fifteen hours after the single treatment (3tumors/timepoint/group), mice are sacrificed and serum is collected for assessment of drug concentrationusing an LC-MS based bioanalytical method 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Lovly CM, et al. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinaseinhibitors. Cancer Res.2011 Jul 15;71(14):4920-31.McePdfHeightCaution: Pr