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.

BRDT BD1:143 nM, BRD4 BD1:41 nM, BRD2 BD1:75 nM, BRD3 BD1:41 nM

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)[1]. 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[1].

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[1].