ARV-825, a heterobifunctional PROTAC (Proteolysis Targeting Chimera) that recruits BRD4 to the E3 ubiquitin ligase cereblon leading to fast, efficient, and prolonged degradation of BRD4 in all BL cell lines tested.

BRD4 BD1:90 nM (Kd), BRD4 BD2:28 nM (Kd)

ARV-825 more effectively suppresses c-MYC levels and downstream signaling than small molecule BRD4 inhibitors resulting in more effective cell proliferation inhibition and apoptosis induction in BL.In Burkitt's lymphoma cells, ARV-825 reduces c-Myc levels, blocks cell proliferation, and induces apoptosis.

Cells (50000/100ul) were seeded in 96-well tissue culture plates followed by addition of ARV-825?at indicated concentration.?After 72 hours, 100 μL per well of reconstituted CellTiter-Glo reagent was added and read on Cytation 3 imaging reader.?Relative cell growth was determined by comparing assay readings of treated cells with control DMSO treated cells.?For apoptosis induction, Caspase-Glo 3/7 Assay was used following manufacturer s instruction.