YU238259 - DNA-PK 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEYU238259Cat. No.: HY-19977CAS No.: 1943733-16-1分式: CHClNOS分量: 459.95作靶点: DNA-PK作通路: Cell Cycle/DNA Damage; PI3K/Akt/mTOR储存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect fromlight)溶解性数据体外实验 DMSO :

2、300 mg/mL (652.24 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.1741 mL 10.8707 mL 21.7415 mL5 mM 0.4348 mL 2.1741 mL 4.3483 mL10 mM 0.2174 mL 1.0871 mL 2.1741 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，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 YU238259种同 依赖性 DNA 修复

3、 (HDR) 抑制剂，可于癌症研究。IC50 & Target HDR 1体外研究YU238259 is an inhibitor of homology-dependent DNA repair, with no effect on PARP activity. YU238259shows cytotoxicity in BRCA2-deficient cells, with a low LD50 of 8.5 M. YU238259 (0-5 M) causes a potent,dose-dependent decrease in HDR efficiency in U2OS DR-GF

4、P or U2OS EJ5-GFP cells, but with no effect on1/2 Master of Small Molecules 您边的抑制剂师www.MedChemENHEJ frequency. YU238259 (0-10 M) exhibits synthetic lethality with loss of frequently mutated tumorsuppressors, and shows synergism with radiotherapy (IR) and DNA-damaging chemotherapy that ispotentiated

5、by BRCA2 loss 1.体内研究 YU238259 (3 mg/kg, i.p.) inhibits the growth of BRCA2-deficient tumor xenografts in nude mice 1.PROTOCOLCell Assay 1 U2OS reporter cell lines (DR-GFP or EJ5-GFP) are pretreated in triplicate with varying concentrations ofYU238259 for 24 h, after which 4 g of SCE-I plasmid is tra

6、nsfected into 1 106 cells/replicate using anAmaxa Nucleofector. Transfected cells are reseeded on 6-well plates and cultured with YU238259 for anadditional 72 h. The percentage of GFP-positive cells is quantified by flow cytometry. Data analysis isperformed using FlowJo software. Error bars represen

7、t the standard deviation 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal 069(nu)/070(nu/+) athymic nude mice, at 4-5 weeks age, are injected subcutaneously with 3 106 DLD-1 orAdministration 1 DLD-1 BRCA2-KO cells suspended in 100 L PBS. Tumor t

8、ake rate is 80%. When tumors reach 100 mm3geometric mean volume, the mice are injected with 3 mg/kg YU238259 or its 3:1 DMSO:PBS vehicle, or 5mg/kg YU128440 or its 1:19 DMSO:PBS vehicle (IP, 100 L total in each case). Treatment is repeated3/week (Mon/Wed/Fri) for a total of 12 doses of YU238259 and

9、4 doses of YU128440. Tumor growth isassessed by external caliper. Mice are euthanized when individual tumor volumes exceed 1000 mm3 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Stachelek GC, et al. YU238259 Is a Novel Inhibitor of Homology-Dependent DNA Repair That Exhibits Synthetic Lethality andRadiosensitization in Repair-Deficient Tumors. Mol Cancer Res. 2015 Oct;13(10):1389-97.McePdfHeightCaution: Product has not been fully validated f