GSK778

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GSK778 是 BD1 溴结构域的有效选择性抑制剂，例如 BRD2 BD1 (IC50s = 75 nM)、BRD3 BD1 (IC50s = 41 nM)、BRD4 BD1 (IC50s = 41 nM) 和 BRDT BD1 (IC50s = 143 nM)。 GSK778 抑制增殖，诱导细胞周期停滞和细胞凋亡。

GSK778 is a potent and selective inhibitor of BD1 bromodomain such as BRD2 BD1 (IC50s = 75 nM), BRD3 BD1 (IC50s = 41 nM), BRD4 BD1 (IC50s = 41 nM), and BRDT BD1 (IC50s = 143 nM). GSK778 inhibits proliferation, induces a cell cycle arrest and apoptosis.(In Vitro):GSK778 phenocopies the effects of pan-BET inhibitors in cancer models. GSK778 inhibits BRD BD2 receptors such as BRD2 BD2 (IC50 = 3950 nM), BRD3 BD2 (IC50 = 1210 nM ), BRD4 BD2 (IC50 = 5843 nM), and BRDT BD2 (IC50 = 17451 nM). GSK778 (0.001-10 μM; 5 days) has a more pronounced effect on the growth and viability of MDA-453, MOLM-13, K562, MV4-11, THP-1, and MDA-MB-231 cells. GSK778 (1000 nM; 12 days) reduces the clonogenic capacity of primary human AML cells. GSK778 (0.01-10 μM; 72 hours) inhibited the production of effector cytokines including IFNγ, IL-17A and IL-22 and the proliferative activity of human primary CD4+ T cells.(In Vivo):GSK778 (15?mg/kg/BID; s.c. for 14 days) reduces the production of anti-keyhole limpet hemocyanin (KLH) IgM and is well tolerated. GSK778 (15?mg/kg/BID; i.p. for 30 days) offers a superior survival advantage to iBET-BD2 in the aggressive MLL-AF9 AML model. The Cmax, Tmax and AUC∞ values are 85 ng/mL, 1.48 h and 132 ng.h/mL, respectively.

GSK778 inhibits BRD BD2 with the IC50s of 3950 nM (BRD2 BD2), 1210 nM (BRD3 BD2), 5843 nM (BRD4 BD2), and 17451 nM (BRDT BD2), respectively.GSK778 (0.01-10 μM; 72 hours) inhibits the proliferative activity of human primary CD4+ T cells and the production of effector cytokines including IFNγ, IL-17A and IL-22.GSK778 (0.001-10 μM; 5 days) has a more pronounced effect on the growth and viability of MDA-453, MOLM-13, K562, MV4-11, THP-1, and MDA-MB-231 cells.GSK778 (1000 nM; 72 hours) inhibits proliferation, induces a cell cycle arrest and apoptosis in MV4-11, MOLM13, MDA-MB-231 and MB453 cells.GSK778 (1000 nM; 12 days) reduces the clonogenic capacity of primary human AML cells. Cell Proliferation Assay Cell 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 Assay Cell 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 Analysis Cell 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.

GSK778 (15mg/kg/BID; i.p. for 30 days) offers a superior survival advantage to iBET-BD2 in the aggressive MLL-AF9 AML model.GSK778 (15mg/kg/BID; s.c. for 14 days) reduces the production of anti-keyhole limpet hemocyanin (KLH) IgM and is well tolerated.GSK778 exhibits Cmax (85 ng/mL), Tmax (1.48 h) and AUC∞ (132 ng.h/mL) following oral administration (10mg/kg) in mice. 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:Cmax (85 ng/mL), Tmax (1.48 h); AUC∞ (132 ng.h/mL).

iBET-BD1

Chromatin/Epigenetic

Epigenetic Reader Domain

VHL

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2451862-42-1

511.61

C30H33N5O3

>98% (HPLC)

In Vitro:?DMSO : 41.67 mg/mL (81.45 mM)

C[C@H](c1ccccc1)n1c2c(cc(c(-c3c(C)onc3C)c3)OC[C@@H]4CNCC4)c3ncc2nc1COC

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(-20℃)

With Ice Pack

≥ 2 years