BETd-246 - BET Protein Degrader - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBETd-246Cat. No.: HY-115568CAS No.: 2140289-17-2分式: CHNO分量: 946.02作靶点: PROTAC; Epigenetic Reader Domain作通路: PROTAC; Epigenetics储存式: -20C, stored under nitrogen* In solvent : -80C, 6 months; -20C, 1 month (stored undernitrogen)溶解

2、性数据体外实验 DMSO : 200 mg/mL (211.41 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.0571 mL 5.2853 mL 10.5706 mL5 mM 0.2114 mL 1.0571 mL 2.1141 mL10 mM 0.1057 mL 0.5285 mL 1.0571 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。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证

3、实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 5 mg/mL (5.29 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 BETd-246第代 BET溴端结构域 (BRD) 的抑制剂，具有良好的选择性、有效性和抗肿瘤活性。1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEIC50 & Target BET BRD 1

4、.体外研究 BETd-246 treatment (0-100 nM, 1-3 h) causes a dose-dependent depletion of BRD2, BRD3 and BRD4 inrepresentative TNBC cell lines with 30-100 nM for 1 h or with 10-30 nM for 3 h incubation.BETd-246 (100 nM, 24/48 hours) displays strong growth inhibition and apoptosis induction activity in MDA-MB-

5、468 cell lines. BETd-246 induces a rapid and time-dependent downregulation of MCL1 protein in all theTNBC cell lines evaluated. BETd-246 induces much stronger apoptosis than BETi-211.BETd-246 (100 nM, 24 hours) induces pronounced cell cycle arrest and apoptosis in TNBC cell lines 1.Cell Proliferatio

6、n Assay 1Cell Line: MDA-MB-468 cellsConcentration: 100 nMIncubation Time: 24 or 48 hoursResult: Displayed strong growth inhibition and apoptosis induction activity in TNBC cell lines.Cell Cycle Analysis 1Cell Line: Human TNBC cellsConcentration: 100 nMIncubation Time: 24 hoursResult: Induced pronoun

7、ced cell cycle arrest and apoptosis in TNBC cell lines.Western Blot Analysis 1Cell Line: Human TNBC cellsConcentration: 0-100 nMIncubation Time: 1-3 hoursResult: Caused a dose-dependent depletion of BRD2, BRD3 and BRD4.体内研究BETd-246 (5 mg/kg, IV, 3 times per week for 3 weeks) treatment effectively in

8、hibits WHIM24 tumor growth,similar to the antitumor activity of BETi-211 with higher dosage and more frequently administration. Thetreatment of 10 mg/kg induces partial tumor regression during treatment without apparent toxicity. BETd-246has very limited drug exposure in the xenograft tumor tissue i

9、n MDA-M-231and MDA-MB-468 models 1.Animal Model: “Washington Human in Mouse (WHIM)” (PDX) model developed from a patient withtreatment-resistant breast cancer (ESRE380Q, PR- and HER2-) 1.Dosage: 5, 10 mg/kg2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEAdministration: IV, 3 times per week for 3 weeks.Result: Effectively inhibited WHIM24 tumor growth.REFERENCES1. Bai L, et al. Targeted Degradation of BET Proteins in Triple-Negative Breast Cancer. Cancer Res. 2017 May 1;77(9):2476-2487.McePdfHeightCaution: Product has not been fully validated