GSK778 (C09-1135-208)

GSK778 (iBET-BD1) is a potent and selective BD1 bromodomain inhibitor of the BET proteins, with IC 50 s of 75 nM ( BRD2 BD1 ), 41 nM ( BRD3 BD1 ), 41 nM ( BRD4 BD1 ), and 143 nM ( BRDT BD1 ), respectively. GSK778 phenocopies the effects of pan- BET inhibitors in cancer modelsIn VitroGSK778 抑制 BRD BD2，IC 50 分别为 3950 nM (BRD2 BD2)、1210 nM (BRD3 BD2)、5843 nM (BRD4 BD2) 和 17451 nM (BRDT BD2)。 GSK778 (0.01-10 μM；72 小时) 抑制人原代 CD4 + T 细胞的增殖活性和效应细胞因子的产生，包括 IFNγ、IL-17A 和 IL-22。 GSK778 (0.001-10 μM；5 天) 对 MDA-453、MOLM-13、K562、MV4-11、THP-1 和 MDA-MB-231 细胞。 GSK778 (1000 nM；72 小时) 在 MV4-11、MOLM13、MDA-MB-231 和 MB453 细胞中抑制增殖，诱导细胞周期停滞和细胞凋亡。 GSK778 (1000 nM；12 天) 降低原代人 AML 细胞的克隆形成能力。 MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell Line: Human primary CD4 + T cell Concentration: 0.001, 0.01, 0.1, 1, 10 μM Incubation Time: 72 hours Result: Inhibited the proliferative activity of the cells and the production of effector cytokines. Cell Viability AssayCell Line: MDA-453, MOLM-13, K562, MV4-11, THP-1, and MDA-MB-231 cells Concentration: 0.001, 0.01, 0.1, 1, 10 μM Incubation Time: 5 days Result: Inhibited the growth and viability of human cancer cell lines. Apoptosis AnalysisCell Line: MV4-11, MOLM13, MDA-MB-231 and MB453 cells Concentration: 1000 nM Incubation Time: 72 hours Result: Inhibited cell proliferation and induced a cell cycle arrest and apoptosis.In VivoGSK778 (15 mg/kg/BID；腹腔注射 30 天) 在侵袭性 MLL-AF9 AML 模型中提供优于 iBET-BD2 的生存优势 。 GSK778 (15 mg/kg/BID；皮下注射 14 天) 减少抗匙孔血蓝蛋白 (KLH) IgM 的产生并且耐受性良好 。 GSK778 表现出 C max (85 ng/mL)、T max (1.48 h) 和 AUC ∞ (132 ng.h/mL) 口服给药 (10 mg/kg) 后在小鼠中 。 MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: 6-8 weeks female C57BL/6 mice are injected with MLL-AF9 cells Dosage: 15 mg/kg/BID Administration: I.p. injections for 30 days Result: Increased the survival rate of leukemia mice. Animal Model: Male CD1 mice Dosage: 10 mg/kg (Pharmacokinetic Analysis) Administration: P.o. administration Result: C max (85 ng/mL), T max (1.48 h); AUC ∞ (132 ng.h/mL).Form:SolidIC50& Target:BRD2 BD1 75 nM (IC 50 ) BRD3 BD1 41 nM (IC 50 ) BRD4 BD1 41 nM (IC 50 ) BRDT BD1 143 nM (IC 50 ). Specification: 0.99 Molecular Formula: C30H33N5O3 Molecular Weight: 511.61