艾力替尼作用机制 - Medchemexpress - MCE中国

1、Product Data SheetAllitinib tosylateCat. No.: HY-13427CAS No.: 1050500-29-2分式: CHClFNOS分量: 621.08作靶点: EGFR作通路: JAK/STAT Signaling; Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (80.50 mM; Need ultrasonic)H2O : 0.1 mg/mL (in

2、soluble)SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 1.6101 mL 8.0505 mL 16.1010 mL5 mM 0.3220 mL 1.6101 mL 3.2202 mL10 mM 0.1610 mL 0.8050 mL 1.6101 mL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；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物

3、和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.03 mM); Clear solution此案可获得 2.5 mg/mL (4.03 mM，饱和度未知) 的澄

4、清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.03 mM); Precipitated solutionPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (4.03 mM，饱和度未知)以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO

5、储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Allitinib tosylate (AST-1306 (TsOH) 种具有服活性且不可逆的 EGFR 和 ErbB2 抑制剂IC50 分别为 0.5 和 3 nM。Allitinib tosylate 抑制 ErbB4，IC50 为 0.8 nM。Allitinib tosylate 种苯胺基喹唑啉化合物，具有抗癌活性。IC & Target EGFR ErbB2 EGFRL858R/T790M ErbB40.5 nM (IC50) 3 nM (IC50) 12 nM (IC50) 0.8 nM (IC5

6、0)体外研究 AST1306 tosylate (AST-1306 (TsOH); 0.19-6.25 M; 72 hours) induces a significant, concentration-dependentinhibition of the growth of HIH3T3-EGFR T790M/L858R cells1.AST1306 tosylate inhibits the activation of tyrosine kinases and downstream signaling pathways in A549 cells, Calu-3cells and SK-O

7、V-3 cells. AST1306 tosylate dose-dependently and markedly inhibits EGF-induced EGFRphosphorylation in A549 cells1.AST1306 tosylate (0.1, 0.5, 1.0, 5.0 M) can dramatically inhibit the growth of both tumor cells on soft agar, and SK-OV-3 cells exhibited much more sensitivity than that of A549 cells1.A

8、ST1306 tosylate (0.001-1.0 M; 4 hours) is more than 3000-fold selective for ErbB family kinases over other kinasefamilies1.AST1306 tosylate potently inhibits the EGFR T790M/L858R double mutant, exhibiting an IC50 value of 122 nmol/L1.Cell Proliferation Assay1Cell Line: NIH3T3 parental cells and NIH3

9、T3 cellsConcentration: 0.19, 0.39, 0.78, 1.56, 3.13, 6.25 MIncubation Time: 72 hoursResult: Induced a significant, concentration-dependent inhibition of the growth of HIH3T3-EGFR T790M/L858R cells.Western Blot Analysis1Cell Line: A549 cells , Calu-3 cells and SK-OV-3 cellsConcentration: 0.001, 0.01,

10、 0.1, 1.0 MIncubation Time: 4 hoursResult: Inhibits the activation of tyrosine kinases and downstream signaling pathways.体内研究AST1306 tosylate (AST-1306 (TsOH); p.o.; 25-100 mg/kg; twice daily; for 28 days) causes a dramatic suppression oftumor growth in SK-OV-3 and Calu-3 xenograft models1.Animal Mo

11、del: Nude mice with SK-OV-3 and Calu-3 tumors1Dosage: 25, 50, 100 mg/kgAdministration: p.o.; twice daily; for 28 daysPage 2 of 3 www.MedChemEResult: Caused a dramatic suppression of tumor growth.REFERENCES1. Xie H, Lin L, Tong L et al. AST1306, a novel irreversible inhibitor of the epidermal growth factor receptor 1 and 2, exhibits antitumor activity both in vitroand in vivo. PLoS One. 2011;6(7):e21487.McePdfHeightCaution: Product has not been fully vali