ZX079 is a potent, selective dual BRD4/CBP PROTAC degrader with DC50 of 0.035 nM and <0.02 nM in MV4-11 cells.
ZX079 induces 95% degradation of BRD4 and 74% of CBP at 2 nM in MV4-11 cells.
ZX079 effectively induces the degradation of BRD3, not BRD2, with a DC50 value less than 0.02 nM.
ZX079 induces BRD4 and CBP degradation through the ubiquitin–proteasome system (UPS).
ZX079 displays potent binding to BRD4 (1), BRD4 (2), and CBP with IC50 values of 0.9, 0.5, and 1.2 μM, respectively, effectively induces the assembly of both BRD4-PROTAC-CRBN and CBP-PROTAC-CRBN complexes.
ZX079 (200 nM) induces a profound and significant depletion of BET/CBP proteins, with BRD4, BRD3, CBP, and p300 levels reduced by 89.3%, 86.2%, 62.5%, and 58.9%, respectively in MV4-11 cells.
ZX079 demonstrates superior efficacy in inhibiting MV4-11 cell proliferation with IC50 of 0.86 nM, compared with NEO2734 and CCS1477, shows minimal cytotoxicity toward normal cells.
potently induces apoptosis in a dose-dependent manner on MV4-11 cells.
ZX079 (10 mg/kg, i.p., qW) exhibited robust antitumor activity on MV4-11 xenograft model.