Y06137 - BET BRD4(1) 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEY06137Cat. No.: HY-111503CAS No.: 2226534-49-0分式: CHNO分量: 444.57作靶点: Epigenetic Reader Domain作通路: 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 : 62.5 mg/mL (140.59 mM; Need ultr

2、asonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (4.68 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (4.68 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Y06137种有效的选择性 BET 抑制剂，与 BRD4(1) 溴结构域结合，Kd 值为 81 nM

3、1。Y06137 于治疗去势抵抗性前列腺癌 (CRPC) 1。IC50 & Target BRD4(1)81 nM (Kd)体外研究 Y06137 (0.001-100 nM, 96 hours for LNCaP, C4-2B, and 22Rv1 cells; 144 hours for VCaP cells) exhibits lowmicromolar or nanomolar potencies (IC50: 0.29-2.6 ) in the four androgen receptor (AR)-positive prostatecancer cell lines LNCaP,

4、C4-2B, 22Rv1, and VCaP. Treatment of 22Rv1 cells with Y06137 (1, 2, 4, 8, and 16M, 48 hours) results in significant down-regulation of both full-length (AR-fl) and AR variants levels 1.Cell Viability Assay 1Cell Line: AR-positive prostate cancer cell lines LNCaP, C4-2B, 22Rv1, and VCaPConcentration:

5、 0.001-100 MIncubation Time: 96 hours for LNCaP, C4-2B, and 22Rv1; 144 hours for VCaPResult: Inhibited LNCaP, C4-2B, 22Rv1, and VCaP cells with IC50s of 0.47, 0.84, 0.70, 0.29 M,respectively.Western Blot Analysis 1Cell Line: AR-positive prostate cancer cell lines 22Rv1Concentration: 1, 2, 4, 8, and

6、16 MIncubation Time: 48 hoursResult: Resulted in significant down-regulation of both AR-fl and AR variants levels.体内研究 Y06137 (50 mg/kg, i.p. injection, 5 times per week, 25 days) demonstrates therapeutic effects in a C4-2BCRPC xenograft tumor model in mice. Y06137 is well tolerated in the treated m

7、ice, based on the weight ofthe animal body and their general behavior 1.Animal Model: Four-week-old male mice (strain: C.B-17/IcrHsd-Prkdcscid for C4-2B) with C4-2B mousexenograft model 1Dosage: 50 mg/kg, 100 LAdministration: Intraperitoneal (i.p.) injection, 5 times per week, 25 daysResult: Exhibit

8、ed strong antitumor activities during the 25-day treatment period, with a tumorgrowth inhibition (TGI) of 51%.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEREFERENCES1. Zhang M, et al. Structure-Based Discovery and Optimization of Benzo disoxazole Derivatives as Potent and Selective BET Inhibitorsfor Potential Treatment of Castration-Resistant Prostate Cancer (CRPC). J Med Chem. 2018 Apr 12;61(7):3037-3058.McePdfHeightCaution: Product has not been fully validated for medical applic