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Updated: Sep 25, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Development of novel androgen receptor antagonists based on the structure of darolutamide
Qian Xu1, Zixiong Zhang2, Chenchao Huang1
1Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, China.
Abstract:
Androgen signaling pathway plays an important role in the occurrence and development of prostate cancer (PCa), and anti-androgen drugs are one of the most effective therapies for PCa. Darolutamide 4 (ODM-201) is a promising second- generation antiandrogen because of its unique chemical structure and good activity against androgen receptor (AR). Herein, the structure-activity relationship of ODM-201 was studied, and 37 analogues were synthesized. Half of them exhibited similar or better anti-AR transcriptional activity compared to ODM-201. In addition, the inhibitory activity of compound 28t against the two resistant mutants (AR-F876L and AR-T877A) was superior to that of ODM-201. This study provides a new clue for the further optimization of ODM-201 and the development of anti-CRPC drugs.
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