PLX-4104 is an orally active BRD4 molecular glue degrader with a DC50 of 2 nM. PLX-4104 selectively promotes BRD4 degradation via DCAF11 recruitment, triggering ubiquitination and proteasomal breakdown. PLX-4104 inhibits cancer cell proliferation. PLX-4104 induces complete regression of AML xenograft tumors. PLX-4104 can be used for the research of acute myeloid leukemia [1].
In Vivo, PLX-4104 (2-6 mg/kg; p.o.; daily; 21 days) elicits dose-dependent antitumor efficacy in AML MV-4-11 xenografts without significant body weight changes[1].
In Vitro, PLX-4104 potently binds to BRD4 with an IC50 of 4 nM[1]. PLX-4104 (24 h) induces near-complete (>95%) BRD4 degradation in MV-4-11 cells with a DC50 of 2 nM[1]. PLX-4104 (72 h) potently inhibits the proliferation of MV-4-11 cells with an EC50 of 4 nM[1]. PLX-4104 has intrinsic clearance of 11.1 mL/min/kg in human liver microsomes and <10 mL/min/kg in mouse liver microsomes[1].
References:
[1]. Leriche G, et al. Discovery and Structural Optimization of BRD4-Selective Monovalent Direct Degraders[J]. ACS Medicinal Chemistry Letters, 2026.
In Vivo, PLX-4104 (2-6 mg/kg; p.o.; daily; 21 days) elicits dose-dependent antitumor efficacy in AML MV-4-11 xenografts without significant body weight changes[1].
In Vitro, PLX-4104 potently binds to BRD4 with an IC50 of 4 nM[1]. PLX-4104 (24 h) induces near-complete (>95%) BRD4 degradation in MV-4-11 cells with a DC50 of 2 nM[1]. PLX-4104 (72 h) potently inhibits the proliferation of MV-4-11 cells with an EC50 of 4 nM[1]. PLX-4104 has intrinsic clearance of 11.1 mL/min/kg in human liver microsomes and <10 mL/min/kg in mouse liver microsomes[1].
References:
[1]. Leriche G, et al. Discovery and Structural Optimization of BRD4-Selective Monovalent Direct Degraders[J]. ACS Medicinal Chemistry Letters, 2026.