dHTC3 is a selective BRD4 molecular glue degrader. dHTC3 selectively binds to BRD4 BD1 to form a BRD4-dHTC3 complex, which cooperatively recruits the SCF FBXO3 E3 ubiquitin ligase and mediates the degradation of BRD4 via the ubiquitin-proteasome pathway. dHTC3 induces proteasome- and CRL-dependent BRD4 degradation with no hook effect. dHTC3 can be used in related research on acute myeloid leukemia [1].
In Vitro, dHTC3 (1 nM-100 μM; 12-16 h) degrades BRD4 in MV4;11 BRD4-HiBiT cells, and pretreatment with JQ1, MLN4924, and Carfilzomib blocks this degradation[1]. dHTC3 does not exhibit the hook effect in both BRD4 degradation and ternary complex formation assays[1]. dHTC3 (1 nM-100 μM; 1-16 h) selectively degrades BRD4 in MV4;11, HEK293T and NALM6 cells via SCFFBXO3 mediation, and its degradation activity is completely abolished after FBXO3 knockout[1].
References:
[1]. Shaum J B, et al. High-throughput ligand diversification to discover chemical inducers of proximity[J]. Nature chemical biology, 2026: 1-13.
In Vitro, dHTC3 (1 nM-100 μM; 12-16 h) degrades BRD4 in MV4;11 BRD4-HiBiT cells, and pretreatment with JQ1, MLN4924, and Carfilzomib blocks this degradation[1]. dHTC3 does not exhibit the hook effect in both BRD4 degradation and ternary complex formation assays[1]. dHTC3 (1 nM-100 μM; 1-16 h) selectively degrades BRD4 in MV4;11, HEK293T and NALM6 cells via SCFFBXO3 mediation, and its degradation activity is completely abolished after FBXO3 knockout[1].
References:
[1]. Shaum J B, et al. High-throughput ligand diversification to discover chemical inducers of proximity[J]. Nature chemical biology, 2026: 1-13.