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