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].

WWL0245 (0-1 μM; 96h) inhibits the proliferation of AR-positive prostate cancer cells, with IC50 values ranging from 0.0159 μM to 10 μM. At [1], it exhibits strong antiproliferative activity against AR-positive cell lines VCaP, LNCaP, and 22Rv1, with IC50 values of 0.016 μM, 0.021 μM, and 0.053 μM, respectively. WWL0245 (1 μM; 24 h) induces time-dependent downregulation of BRD4 and c-Myc in LNCaP, 22Rv1, and VCaP cell lines, resulting in concentration-dependent decreases in BRD4 and c-Myc levels in 22Rv1 and VCaP cells. WWL0245 also reduces BRD4 levels in DU145 cells, but its effect on c-Myc levels is negligible [1]. Additionally, WWL0245 (100 nM-1 μM; 24h) suppresses the transcription of AR-regulated genes (PSA, TMPRSS2, ERG, FKBP5, BMPR1B) to varying degrees [1].