PROTAC BRD4 Degrader-6

PROTAC BRD4 Degrader-6 (compound 32a) is a potent small-molecule BRD4 degrader with IC50 value of 2.7 nM for BRD4 BD1. PROTAC BRD4 Degrader-6 potently degrades BRD4 protein and inhibits the expression of c-Myc. PROTAC BRD4 Degrader-6 inhibits the proliferation of pancreatic cancer cell line BxPC3 and induces apoptosis. PROTAC BRD4 Degrader-6 can be used for human pancreatic cancer research[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Apoptosis >> Caspase

Signaling Pathways >> Apoptosis >> c-Myc

Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

BRD4 BD1:2.7 μM (IC50)

Caspase 3

PROTAC BRD4 Degrader-6 (compound 32a) (72 hours; BxPC3 cell) has anti-proliferation activity with IC50 value of 0.165 μM[1]. PROTAC BRD4 Degrader-6 (compound 32a) (1 μM; 48 hours; BxPC3 cell) induces BRD4 protein degradation in a time-dependent manner, which results in the continuous decrease of c-Myc expression[1]. PROTAC BRD4 Degrader-6 (compound 32a) (1 μM; 48 hours; BxPC3 cell) induces the cell cycle arrest and apoptosis[1]. Western Blot Analysis[1] Cell Line: BxPC3 cell Concentration: 1 μM Incubation Time: 48 hours Result: Degraded BRD4 protein in a time-dependent manner and inhibits the expression of c-Myc. Cell Cycle Analysis[1] Cell Line: BxPC3 cell Concentration: 1 μM Incubation Time: 48 hours Result: Increase in G0/G1 and G2/M phase cells, and a decrease of S phase cells. Apoptosis Analysis[1] Cell Line: BxPC3 cell Concentration: 1 μM Incubation Time: 48 hours Result: The percentage of cells in early and late apoptosis was recorded as 10.10% and 12.36%, respectively. Western Blot Analysis[1] Cell Line: BxPC3 cell Concentration: 1 μM Incubation Time: 48 hours Result: The expression of caspase 3 and cleaved-caspase 3 significantly increased.

[1]. Zhang J, et al. Development of small-molecule BRD4 degraders based on pyrrolopyridone derivative. Bioorg Chem. 2020 Jun;99:103817.