WWL0245 is a potent and selective BRD4-targeting PROTAC that exhibits sub-nanomolar degradation efficiency (DC50 < 1 nM) for BRD4 over BRD2/3 and PLK1 (DC50 > 1 μM). It demonstrates pronounced selective cytotoxicity in BETi-sensitive cancer cell lines, particularly in AR-positive prostate cancer lines, making it a promising candidate for research in AR-positive prostate cancer and a valuable tool for the investigation of BRD4's biological function [1].

BRD4:1 nM

WWL0245 (0-1 μM; 96小时) 对AR阳性前列腺癌细胞具有显著的增殖抑制作用，IC50值在0.0159 μM至10 μM之间。特别是在[1]条件下，对AR阳性的VCaP、LNCaP和22Rv1细胞株表现出较高的抗增殖活性，其IC50值分别为0.016 μM、0.021 μM和0.053 μM。经WWL0245 (1 μM; 24小时) 处理后，LNCaP、22Rv1和VCaP细胞系中的BRD4和c-Myc蛋白表达呈现时间依赖性减少，而且22Rv1与VCaP细胞中BRD4和c-Myc的水平也表现出浓度依赖性降低。此外，WWL0245能够降低DU145细胞中的BRD4水平，对c-Myc的影响则相对较小[1]。WWL0245 (100 nM-1 μM; 24小时) 对AR调控基因（PSA、TMPRSS2、ERG、FKBP5、BMPR1B）的转录活性产生不同程度的抑制作用[1]。