2023年12月28日 · Bromodomain-containing protein 4 (BRD4) has been a new potential drug target for PCa treatment. Herein, we report the rational design and discovery of novel BRD4 inhibitors through computer-aided drug design (CADD), and a hit compound SQ-1 (IC 50 = 676 nM) was identified by structure-based virtual screening (SBVS) with the conserved water network.

2014年4月23日 · Here we show that AR-signalling-competent human CRPC cell lines are preferentially sensitive to bromodomain and extraterminal (BET) inhibition. BRD4 physically interacts with the N-terminal...

2019年9月16日 · Bromodomain (BRD) and extra-terminal motif (BET) protein inhibitors have been shown to attenuate AR signaling in metastatic castration-resistant prostate cancer and to overcome enzalutamide...

在雄激素受体 (AR)表达阳性的前列腺癌中,转录辅因子BRD4可以与AR相互作用并影响下游基因的转录,调控MYC,PSA,TMPRSS2-ERG融合基因等的表达,从而促进前列腺癌细胞的增殖,并与前列腺癌的去势抵抗,转移及不良预后密切相关,因此BRD4可作为AR-阳性前列腺癌的潜在治疗靶点.但传统的BRD4抑制剂往往选择性不佳,对BET家族蛋白包括BRD2,BRD3及BRDT均有不同程度的抑制活性,因此容易引起多种毒副反应;且药物作用时间不够持久,病人容易产生耐药.能够选择性持续下 …

Upregulated BRD4 is associated with HIF-1α and acetylated histones and binds to AR promoter, activating AR transcription. Selective BRD4 inhibitor JQ1 suppresses BRD4 activity and downregulates AR, resulting in the amelioration of ovarian fibrosis and ovarian function.

2025年1月22日 · In prostate adenocarcinomas, BRD4 associates with AR and is recruited to AR target genes, thus activating AR signaling pathways for growth and survival of adenocarcinoma cells 26. Recently, a study reported that BRD4 functions with E2F1 to regulate cell cycle associated programs and that BRD4 inhibitors decrease growth of tumor models 27 .

In this study, AR activation in dehydroepiandrosterone- and letrozole-induced rat PCOS ovaries coincided with a marked increase of a chromatin acetylation ‘‘reader’’ BRD4. Further bioinformatic analysis showed that the promoter contained highly conserved binding motifs of BRD4 and HIF-1a. BRD4 and HIF-1 inducibly.

2020年1月22日 · Analyses of RNA expression and chromatin immunoprecipitation followed by sequencing revealed that ABBV-744 displaced BRD4 from AR-containing super-enhancers and inhibited AR-dependent...

12a (WWL0245) is a potent and highly selective BRD4-PROTAC. 12a exhibited better antiproliferative activity in AR-positive prostate cancer cells than WNY0824. BRD4-targeted proteolysis targeting chimera (PROTAC) have exhibited promising in vitro and in vivo anticancer activity in a number of cancer models.

在雄激素受体（ar）表达阳性的前列腺癌中，转录辅因子brd4可以与ar相互作用并影响下游基因的转录，调控myc、psa、tmprss2-erg融合基因等的表达，从而促进前列腺癌细胞的增殖，并与前列腺癌的去势抵抗、转移及不良预后密切相关，因此brd4可作为ar-阳性前列腺癌 ...