BRD4 degrader AT1

BRD4 degrader AT1 is a PROTAC connected by ligands for von Hippel-Lindau and BRD4 as a highly selective Brd4 degrader, with a K_d of 44 nM for Brd4^BD2 in cells. IC50 & Target:Kd: 44 nM (Brd4^BD2, cell assay), 38.8 nM (Brd4^BD2 QVK, cell assay), 111 nM (Brd2^BD1, cell assay), 94 nM (Brd2^BD2, cell assay), 35 nM (Brd3^BD1, cell assay), 39 nM (Brd3^BD2, cell assay), 75 nM (Brd4^BD1, cell assay), 35 nM (Brd2^BD1 KEA, cell assay)^[1] In Vitro: BRD4 degrader AT1 is a highly selective Brd4 degrader, with a K_d of 44 nM, for Brd4^BD2 in cells. BRD4 degrader AT1 also shows K_ds of 38.8 nM for a mutant Brd4^BD2 (QVK), 111 ± 14 nM for Brd2^BD1, 94 ± 9 nM for Brd2^BD2, 35 ± 3 nM for Brd3^BD1, 39 ± 8 nM for Brd3^BD2, 75 ± 23 nM for Brd4^BD1 and 35 ± 4 nM for a Brd2^BD1 mutant (KEA). BRD4 degrader AT1 (1-3 μM) causes remarkable Brd4-selective depletion and has no or little activity against Brd2 and Brd3^[1].