CCT367766 formic is a potent third-generation heterobifunctional Cereblon-based protein degradation probe (PDP, or PROTAC) that selectively targets pirin for degradation, effectively diminishing its protein expression at low concentrations. This compound demonstrates moderate affinity towards the CRBN-DDB1 complex, as denoted by an IC50 value of 490 nM, while exhibiting strong binding to recombinant pirin and CRBN, with respective Kd values of 55 nM and 120 nM. As such, CCT367766 formic serves as a valuable chemical probe for investigating the functions of the largely unexplored pirin protein [1].

CRBN-DDB1:490 nM

CCT367766 formic在不同浓度（0.5-1500 nM；24小时）处理下，展现了与时间依赖性挂钩效应相关的pirin蛋白质消耗现象，特别是在SK-OV-3人类卵巢癌细胞中观察到[1]。在低浓度（0.5-50 nM；2小时）处理下，CCT367766 formic也显示了浓度依赖性地减少pirin蛋白表达[1]。此外，CCT367766 formic还能在同浓度和暴露时长（0.5-50 nM；2小时）条件下，对chlorobisamide预处理导致的pirin表达下调产生剂量依存性反救效应[1]。