eCF506 - Src 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEeCF506Cat. No.: HY-112096CAS No.: 1914078-41-3分式: CHNO分量: 510.63作靶点: Src作通路: 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 : 62.5 mg/mL (122.40 mM; Need ultrasoni

2、c)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (4.07 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (4.07 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/2 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.08 mg/mL (4.07 m

3、M); Clear solutionBIOLOGICAL ACTIVITY物活性 eCF506效，有服活性的受体酪氨酸激酶 Src 的抑制剂， IC50 值于0.5 nM。IC50 & Target IC50: less than 0.5 nM (Src) 1体外研究 eCF506 induces a very potent antiproliferative effect in both MCF7 and MDA-MB-231 cells. eCF506 inhibitsphosphorylation of SRC and FAK at low nanomolar levels, with

4、complete inhibition observed at 100 nM.eCF506 significantly reduces cell motility at 10 nM as early as 6 h into the study, with equivalent efficacy todasatinib. eCF506 exclusively inhibits SFK, with subnanomolar IC50 values against SRC and YES(IC50=0.5, 2.1 nM). It is important to highlight that eCF

5、506 displays a vast difference in activity (950-folddifference) between ABL and its primary target SRC 1.体内研究 eCF506 shows a moderate oral bioavailability (25.3%). A significant reduction of phospho-SRCY416 isobserved in the xenograft sections from mice treated with eCF506 relative to the untreated

6、animal controls1.PROTOCOLCell Assay 1 MDA-MB-231 cells are treated with eCF506 or dasatinib (10 nM), and cell migration compared with untreatedcell control (DMSO, 0.1%, v/v) at 6, 12, and 24 h. Cells are imaged and analyzed using an IncuCyte-ZOOMmicroscope with integrated scratch-wound migration sof

7、tware module 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 In vivo PD study is performed in a xenograft model of HCT116 cells in mice. HCT116 cells are injectedsubcutaneously, and tumors are allowed to grow up to 3-mm i

8、n diameter. Subsequently, mice are doseddaily for 3 d with eCF506 (50 mg/kg, in nanopure water) or vehicle (nanopure water) by oral gavage andculled 3 h after the last dose (n=4). Tumors are excised, fixed, and sections labeled for phospho-SRCY416and stained with hematoxylin 1.MCE has not independen

9、tly confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Fraser C, et al. Rapid Discovery and Structure-Activity Relationships of Pyrazolopyrimidines That Potently Suppress Breast Cancer CellGrowth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase. J Med Chem. 2016 May 26;59(10):4697-710.McePdfHeightCaution: Product has not been fully validated for med