dBET6

一种能够诱导BRD4降解的PROTAC（蛋白降解靶向嵌合体）；它能够结合BRD4（IC50=14nM），并在100nM浓度下诱导其降解，从而在MOLT-4细胞中实现对转录的全面抑制。此外，该化合物在MOLT-4 T-ALL小鼠异种移植模型中表现出显著的抗白血病效果，当以7.5mg/kg的剂量每日两次给药时，可显著减少白血病负荷。A PROTAC that drives BRD4 degradation; binds to BRD4 (IC50 = 14 nM) and induces its degradation at 100 nM, leading to a global inhibition of transcription in MOLT-4 cells; reduces leukemic burden in a MOLT-4 T-ALL mouse xenograft model when administered at a dose of 7.5 mg/kg twice per day.分子式C42H45ClN8O7S分子量841.4CC1=NN=C2[C@H](CC(NCCCCCCCCNC(COC3=CC=CC(C(N4C5C(NC(CC5)=O)=O)=O)=C3C4=O)=O)=O)N=C(C6=CC=C(Cl)C=C6)C7=C(SC(C)=C7C)N21