Targeting castration-resistant prostate cancer with a novel RORγ antagonist elaiophylin

Jianwei Zheng, Junfeng Wang, Qian Wang, Hongye Zou, Hong Wang, Zhenhua Zhang, Jianghe Chen, Qianqian Wang, Panxia Wang, Yueshan Zhao, Jing Lu, Xiaolei Zhang, Songtao Xiang, Haibin Wang, Jinping Lei, Hong Wu Chen, Peiqing Liu, Yonghong Liu, Fanghai Han, Junjian Wang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Prostate cancer (PCa) patients who progress to metastatic castration-resistant PCa (mCRPC) mostly have poor outcomes due to the lack of effective therapies. Our recent study established the orphan nuclear receptor RORγ as a novel therapeutic target for CRPC. Here, we reveal that elaiophylin (Elai), an antibiotic from Actinomycete streptomyces, is a novel RORγ antagonist and showed potent antitumor activity against CRPC in vitro and in vivo. We demonstrated that Elai selectively binded to RORγ protein and potently blocked RORγ transcriptional regulation activities. Structure–activity relationship studies showed that Elai occupied the binding pocket with several key interactions. Furthermore, Elai markedly reduced the recruitment of RORγ to its genomic DNA response element (RORE), suppressed the expression of RORγ target genes AR and AR variants, and significantly inhibited PCa cell growth. Importantly, Elai strongly suppressed tumor growth in both cell line based and patient-derived PCa xenograft models. Taken together, these results suggest that Elai is novel therapeutic RORγ inhibitor that can be used as a drug candidate for the treatment of human CRPC.

Original languageEnglish (US)
Pages (from-to)2313-2322
Number of pages10
JournalActa Pharmaceutica Sinica B
Issue number12
StatePublished - Dec 2020


  • Antagonist
  • Castration-resistant prostate cancer
  • Elaiophylin
  • Nuclear receptor
  • RORγ

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)


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