BRD4 Inhibitor-20

BRD4 Inhibitor-20 is a potent orally active bromodomain protein 4 (BRD4) inhibitor. BRD4 Inhibitor-20 has inhibitory activity for BRD4 (BD1) and BRD4 (BD2) with IC50 values of 19 nM and 28 nM, respectively. BRD4 Inhibitor-20 also has anti-proliferation activities in cancer cell lines. BRD4 Inhibitor-20 can be used for the research of kinds of cancer, such as colon cancer[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

BRD4 BD1:19 nM (IC50)

BRD4 BD2:28 nM (IC50)

BRD2 (BD1):24 nM (IC50)

BRD2 (BD2):18 nM (IC50)

BRD4 Inhibitor-20 (compound 12j) exhibits excellent BRD4 inhibitory activities (BD1, IC50=19 nM; BD2, IC50=28 nM) and inhibitory activities against BRD2 (BD1, IC50=24 nM; BD2, IC50=18 nM)[1]. BRD4 Inhibitor-20 (0.5, 2.5, 5.0 μM; 24 h) reduces the expression of c-Myc[1]. BRD4 Inhibitor-20 (72 h) has anti-proliferation potency with IC50 values of 4.75 μM, 1.35 μM and 44.07 μM in HT-29, HL-60 and WI-38 cells, respectively[1]. BRD4 Inhibitor-20 (2.5, 5.0, 10.0 μM; 24 h) can arrest the cell-cycle progression of HT-29 cells into the G1 phase[1]. Western Blot Analysis[1] Cell Line: HT-29 cells Concentration: 0.5, 2.5, 5.0 μM Incubation Time: 24 h Result: Displayed profound inhibitory effects on c-Myc protein expression. Cell Proliferation Assay[1] Cell Line: HT-29, HL-60 and WI-38 cells Concentration: Incubation Time: 72 h Result: Possessed strong anti-proliferative activity and weak toxicity. Cell Cycle Analysis[1] Cell Line: HT-29 cell lines Concentration: 2.5, 5.0, 10.0 μM Incubation Time: 24 h Result: Arrested the cell-cycle progression of the cell line into the G1 phases and the percentage of cells in G1 phase after treatment under concentrations of 2.5, 5.0 and 10.0 μM were 85.98%, 86.49% and 86.05%, respectively.

BRD4 Inhibitor-20 (compound 12j) (i.v., 5 mg/kg; p.o, 15mg/kg) exhibits favorable oral pharmacokinetic propertie[1]. Animal Model: rats[1] Dosage: 5 mg/kg, 15 mg/kg Administration: intravenous dosing (iv) or oral dosing (po) Result: PK Parameters iv (5 mg/kg) po (15 mg/kg) Cmax(μg/L) - 2175 Tmax(h) - 1.00 t1/2(h) 1.56 3.59 CLz/F (L/h/kg) 0.68 1.03 AUC0−t(μg/L*h) 7296 14384 AUC0−∞(μg/L*h) 7340 14600 F (%) - 66%

[1]. Yu Xu, et al. Design, synthesis and biological evaluation of indole-2-one derivatives as potent BRD4 inhibitors. Eur J Med Chem. 2020 Dec 15;208:112780.