典型文献
The novel indomethacin derivative CZ-212-3 exerts antitumor effects on castration-resistant prostate cancer by degrading androgen receptor and its variants
文献摘要：
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.
文献关键词：
中图分类号：
作者姓名：
Hong Wang;Zhe Chang;Guo-di Cai;Ping Yang;Jiang-he Chen;Shan-shu Yang;Yin-feng Guo;Ming-yu Wang;Xue-hua Zheng;Jin-ping Lei;Pei-qing Liu;De-peng Zhao;Jun-jian Wang
作者机构：
School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China;State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Guangzhou 510060,China;Department of Pathology,Sun Yat-sen University Cancer Center,Guangzhou 510060,China;Key Laboratory of Molecular Target and Clinical Pharmacology,School of Pharmaceutical Sciences and the Fifth Affiliated Hospital,Guangzhou Medical University,Guangzhou 510006,China;Guangdong Provincial Key Laboratory of New Drug Design and Evaluation,School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China;National-Local Joint Engineering Laboratory of Druggability and New Drugs Evaluation,Sun Yat-sen University,Guangzhou 510006,China
文献出处：
引用格式：
[1]Hong Wang;Zhe Chang;Guo-di Cai;Ping Yang;Jiang-he Chen;Shan-shu Yang;Yin-feng Guo;Ming-yu Wang;Xue-hua Zheng;Jin-ping Lei;Pei-qing Liu;De-peng Zhao;Jun-jian Wang-.The novel indomethacin derivative CZ-212-3 exerts antitumor effects on castration-resistant prostate cancer by degrading androgen receptor and its variants)[J].中国药理学报（英文版）,2022(04):1024-1032
A类：
indomethacin,Indomethacin,benzoylindole
B类：
novel,CZ,exerts,antitumor,effects,castration,resistant,prostate,cancer,by,degrading,androgen,receptor,variants,Androgen,serves,main,therapeutic,target,PCa,However,resistance,therapy,SAT,inevitably,occurs,nonsteroidal,inflammatory,drug,that,exhibits,activity,against,Recently,designed,synthesized,series,new,derivatives,compounds,Pd,catalyzed,synthesis,substituted,this,study,evaluated,these,CRPC,Upon,employing,CCK,cell,viability,assays,colony,formation,found,had,high,efficacy,growth,vitro,Among,exhibited,most,potent,survival,apoptosis,induction,Mechanistically,significantly,suppressed,expression,gene,networks,Consistently,inhibited,line,xenograft,PDX,models,vivo,Taken,together,data,show,could,promising,agent
AB值：
0.498293
相似文献
机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
