Details

Autor(en) / Beteiligte

• Wang, Xin-Yue
• Chai, Xin
• Shan, Lu-Hu
• Xu, Xiao-Hong
• Xu, Lei
• Hou, Ting-Jun
• Sun, Hui-Yong
• Li, Dan

Titel

A potent new-scaffold androgen receptor antagonist discovered on the basis of a MIEC-SVM model

Ist Teil von

• Acta pharmacologica Sinica, 2024-05, Vol.45 (9), p.1978-1991

Ort / Verlag

United States

Erscheinungsjahr

2024

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Prostate cancer (PCa) is the second most prevalent malignancy among men worldwide. The aberrant activation of androgen receptor (AR) signaling has been recognized as a crucial oncogenic driver for PCa and AR antagonists are widely used in PCa therapy. To develop novel AR antagonist, a machine-learning MIEC-SVM model was established for the virtual screening and 51 candidates were selected and submitted for bioactivity evaluation. To our surprise, a new-scaffold AR antagonist C2 with comparable bioactivity with Enz was identified at the initial round of screening. C2 showed pronounced inhibition on the transcriptional function (IC  = 0.63 μM) and nuclear translocation of AR and significant antiproliferative and antimetastatic activity on PCa cell line of LNCaP. In addition, C2 exhibited a stronger ability to block the cell cycle of LNCaP than Enz at lower dose and superior AR specificity. Our study highlights the success of MIEC-SVM in discovering AR antagonists, and compound C2 presents a promising new scaffold for the development of AR-targeted therapeutics.