| 袁善文#,展伟,代高鑫,等.新型AR-NTD抑制剂设计、合成及生物活性评价[J].中国海洋药物,2026,(3):-. |
| 新型AR-NTD抑制剂设计、合成及生物活性评价 |
| Design, Synthesis, and Biological Evaluation of Novel Androgen Receptor N-Terminal Domain (AR-NTD) Inhibitors |
| 投稿时间：2025-03-12 修订日期：2025-04-11 |
| DOI： |
| 中文关键词: 雄激素受体 EPI-002 前列腺癌 CRPC |
| English Keywords:androgen receptor EPI-002 Prostate cancer CRPC |
| Fund Project: |
|
| 摘要点击次数: 13 |
| 全文下载次数: 0 |
| 中文摘要: |
| 本研究以EPI-002为先导化合物,针对雄激素受体氨端结构域(AR-NTD)设计并合成了一系列衍生物(Y01-Y08),旨在提高其生物活性。采用化学合成方法,引入酰胺、磺酰胺、哌等结构片段。优化分子核心骨架后得到的衍生物Y05(LNCaP, IC50 = 6.89 μM; VCaP, IC50 = 5.77 μM)活性较EPI-002 (LNCaP, IC50=57.98 μM; VCaP, IC50=40.03 μM)活性显著提升,并且Y05可以抑制AR对下游靶基因的转录激活作用。本研究为开发新型AR-NTD抑制剂提供了重要思路,为去势抵抗性前列腺癌(CRPC)的治疗提供新策略。 |
| English Summary: |
| This study investigated EPI-002 as the lead compound and designed and synthesized a series of derivatives (Y01-Y08) that specifically target the N-terminal domain (NTD) of the androgen receptor (AR) to enhance biological activity. The derivatives were synthesized through various chemical methods, incorporating structural fragments such as amides, sulfonamides, and piperidines. After optimizing the core molecular skeleton, derivative Y05 exhibited significantly improved activity compared to EPI-002. Notably, in LNCaP cells, the IC50 value for Y05 was 6.89 μM, whereas that for EPI-002 was 57.98 μM; in VCaP cells, the IC50 value for Y05 was 5.77 μM, compared to 40.03 μM for EPI-002. Additionally, Y05 was able to inhibit the transcriptional activation of downstream target genes by AR. This study provides critical insights into the development of novel AR-NTD inhibitors and introduces new strategies for the treatment of castration-resistant prostate cancer (CRPC). |
| 查看/发表评论 下载PDF阅读器 |
|
| 关闭 |
|
|
|