dBET6 - PROTAC 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEdBET6Cat. No.: HY-112588CAS No.: 1950634-92-0分式: CHClNOS分量: 841.37作靶点: PROTAC; Epigenetic Reader Domain作通路: PROTAC; Epigenetics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 : 100 mg/mL (118

2、.85 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 3 mg/mL (3.57 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 3 mg/mL (3.57 mM); Clear solution1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 dBET6种效的，选择性的，细胞透过的基于 PROTAC 技术的 BET 降解剂，IC50 值为 14 nM，具有

3、抗肿瘤活性。IC50 & Target IC50: 14 nM (BET) 1体外研究 dBET6 is a highly potent, selective and cell-permeable degrader of BET with an IC50 of 14 nM. dBET6 (100nM) exhibits antitumor activity against T cell acute lymphoblastic leukemia (T-ALL) lines via degradation ofBRD4 1.体内研究 dBET6 (7.5 mg/kg, p.o., BID) red

4、uces the leukemic burden in a disseminated mouse model of T-ALL 1.PROTOCOLAnimal Mice 1Administration 1 MOLT4 human T-ALL cells are intravenously injected into NSG mice (2106 cells/mouse). Luminescence isutilized to monitor engraftment (evident at day 6), at which point mice are randomized into thre

5、e cohorts thatreceive dBET6 (7.5 mg/kg BID, n = 8), JQ1 (20 mg/kg QD, n = 9) or vehicle (captisol, n = 9) treatment for 14days. Survival of all three cohorts is subsequently monitored using hind limb paralysis caused by highfemoral leukemic burden as a defined endpoint. SUPT11 human T-ALL cells (mCh

6、erry+ and Luciferase+) areintravenously injected into NSG mice (2.52106 cells/mouse). Luminescence is used to monitor successfulengraftment, occurring 10 days after injection. At this point, animals are randomized into three cohorts thatreceive dBET6 (7.5 mg/kg BID, n = 7), JQ1 (7.5 mg/kg BID, n = 7

7、) or vehicle (captisol, n = 7) treatment for 18days. Treatment burden is assessed via total body luminescence imaging as well as by bone marrowinfiltration by mCherry+ T-ALL cells 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Winter GE, et al. BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment.Mol Cell. 2017 Jul 6;67(1):5-18.e19.McePdfHeightCaution: Product has not been fully validated for medical applications.For re