ARV-825, dubbed as PROTAC (Proteolysis Targeting Chimera), is a potent and selective protein BRD4 degrader with DC50 value of <1 nM. It is a hetero-bifunctional molecule consisting of two high-affinity binding ligands, Thienodiazepine for BRD4 and Phthalimide for E3 ubiquitin ligase cereblon (CRBN), linked by a spacer. Bindings of two ligands to their respective receptors recruit the target protein BRD4 to the E3 ubiquitin ligase cereblon, leading to fast, efficient, and prolonged degradation of BRD4 in all BL cell lines tested. Consequently, ARV-825 suppresses more effectively c-MYC levels and downstream signaling than small-molecule BRD4 inhibitors, resulting in more effective cell proliferation inhibition and apoptosis induction in BL.

KEYWORDS: ARV-825 | BRD4 degrader | ARV825 | ARV 825 | CT-ARV825 | CAS [1818885-28-7] | Histone | BET (BRD) | Degrader | Proteins | PROTAC