@article{APS10540,
author = {Hong Wang and Zhe Chang and Guo-di Cai and Ping Yang and Jiang-he Chen and Shan-shu Yang and Yin-feng Guo and Ming-yu Wang and Xue-hua Zheng and Jin-ping Lei and Pei-qing Liu and De-peng Zhao and Jun-jian Wang},
title = {The novel indomethacin derivative CZ-212-3 exerts antitumor effects on castration-resistant prostate cancer by degrading androgen receptor and its variants},
journal = {Acta Pharmacologica Sinica},
volume = {43},
number = {4},
year = {2022},
keywords = {},
abstract = {Androgen receptor (AR) serves as a main therapeutic target for prostate cancer (PCa). However, resistance to anti-androgen therapy (SAT) inevitably occurs. Indomethacin is a nonsteroidal anti-inflammatory drug that exhibits activity against prostate cancer. Recently, we designed and synthesized a series of new indomethacin derivatives (CZ compounds) via Pd (II)-catalyzed synthesis of substituted N-benzoylindole. In this study, we evaluated the antitumor effect of these novel indomethacin derivatives in castration- resistant prostate cancer (CRPC). Upon employing CCK-8 cell viability assays and colony formation assays, we found that these derivatives had high efficacy against CRPC tumor growth in vitro. Among these derivatives, CZ-212-3 exhibited the most potent efficacy against CRPC cell survival and on apoptosis induction. Mechanistically, CZ-212-3 significantly suppressed the expression of AR target gene networks by degrading AR and its variants. Consistently, CZ-212-3 significantly inhibited tumor growth in CRPC cell line-based xenograft and PDX models in vivo. Taken together, the data show that the indomethacin derivative CZ-212-3 significantly inhibited CRPC tumor growth by degrading AR and its variants and could be a promising agent for CRPC therapy.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10540}
}