A novel inhibitor of ARfl and ARv7 induces protein degradation to overcome enzalutamide resistance in advanced prostate cancer

Li, Yan; Chu, Ya; Shi, Guangjiang; Wang, Xiaobin; Ye, Wanli; Shan, Chun; Wang, Dajia; Zhang, Di; He, Wei; Jiang, Jingwei; Ma, Shuqian; Yue-hong, Han; Zhao, Zhili; Du, Shijia; Chen, Zhe; Li, Zhiyu; Yang, Yong; Wang, Chen; Xu, Xi; Wu, Hongxi

doi:10.1016/j.apsb.2022.05.003

Cited by 1 publication

(2 citation statements)

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“…In vivo pharmacodynamics showed that intravenous administration of 25 mg/kg 72 significantly inhibited the proliferation of 22Rv1 and Enzalutamide-resistant LNCaP xenografts and overcame the neurotoxic effect brought about by Enzalutamide. Unfortunately, the oral bioavailability of 72 needs to be further improved, and its degradation mechanism for AR-V7 deserves more explicit clarification …”

Section: Mechanism-based Classification Of Ar Degradersmentioning

confidence: 99%

“…168 By performing skeleton fusion on the Unfortunately, the oral bioavailability of 72 needs to be further improved, and its degradation mechanism for AR-V7 deserves more explicit clarification. 169 Other compounds disturb the stability of AR through indirect pathways (Figure 27). Interference with HSP90 and histone deacetylase (HDAC) are two recorded approaches to induce degradation.…”

Section: Natural Productsmentioning

confidence: 99%

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A Comprehensive Overview of Small-Molecule Androgen Receptor Degraders: Recent Progress and Future Perspectives

Luo

Xiang

2022

J. Med. Chem.

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Prostate cancer (PC), the second most prevalent malignancy in men worldwide, has been proven to depend on the aberrant activation of androgen receptor (AR) signaling. Longterm androgen deprivation for the treatment of PC inevitably leads to castration-resistant prostate cancer (CRPC) in which AR remains a crucial oncogenic driver. Thus, there is an urgent need to develop new strategies to address this unmet medical need. Targeting AR for degradation has recently been in a vigorous development stage, and accumulating clinical studies have highlighted the benefits of AR degraders in CRPC patients. Herein, we provide a comprehensive summary of small-molecule AR degraders with diverse mechanisms of action including proteolysis-targeting chimeras (PROTACs), selective AR degraders (SARDs), hydrophobic tags (HyT), and other AR degraders with distinct mechanisms. Accordingly, their structure− activity relationships, biomedical applications, and therapeutic values are also dissected to provide insights into the future development of promising AR degradation-based therapeutics for CRPC.

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Section: Mechanism-based Classification Of Ar Degradersmentioning

confidence: 99%

Section: Natural Productsmentioning

confidence: 99%