典型文献
Discovery of a novel nonsteroidal selective glucocorticoid receptor modulator by virtual screening and bioassays
文献摘要：
Synthetic glucocorticoids(GCs)have been widely used in the treatment of a broad range of inflammatory diseases,but their clinic use is limited by undesired side effects such as metabolic disorders,osteoporosis,skin and muscle atrophies,mood disorders and hypothalamic-pituitary-adrenal(HPA)axis suppression.Selective glucocorticoid receptor modulators(SGRMs)are expected to have promising anti-inflammatory efficacy but with fewer side effects caused by GCs.Here,we reported HT-15,a prospective SGRM discovered by structure-based virtual screening(VS)and bioassays.HT-15 can selectively act on the NF-KB/AP1-mediated transrepression function of glucocorticoid receptor(GR)and repress the expression of pro-inflammation cytokines(i.e.,IL-1 β,IL-6,COX-2,and CCL-2)as effectively as dexamethasone(Dex).Compared with Dex,HT-15 shows less transactivation potency that is associated with the main adverse effects of synthetic GCs,and no cross activities with other nuclear receptors.Furthermore,HT-15 exhibits very weak inhibition on the ratio of OPG/RANKL.Therefore,it may reduce the side effects induced by normal GCs.The bioactive compound HT-15 can serve as a starting point for the development of novel therapeutics for high dose or long-term anti-inflammatory treatment.
文献关键词：
中图分类号：
作者姓名：
Jin-ping Pang;Xue-ping Hu;Yun-xia Wang;Jia-ning Liao;Xin Chai;Xu-wen Wang;Chao Shen;Jia-jia Wang;Lu-lu Zhang;Xin-yue Wang;Feng Zhu;Qin-jie Weng;Lei Xu;Ting-jun Hou;Dan Li
作者机构：
Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;State Key Lab of CAD&CG,Zhejiang University,Hangzhou 310058,China;Institute of Bioinformatics and Medical Engineering,School of Electrical and Information Engineering,Jiangsu University of Technology,Changzhou 213001,China;Center for Drug Safety Evaluation and Research,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China
文献出处：
引用格式：
[1]Jin-ping Pang;Xue-ping Hu;Yun-xia Wang;Jia-ning Liao;Xin Chai;Xu-wen Wang;Chao Shen;Jia-jia Wang;Lu-lu Zhang;Xin-yue Wang;Feng Zhu;Qin-jie Weng;Lei Xu;Ting-jun Hou;Dan Li-.Discovery of a novel nonsteroidal selective glucocorticoid receptor modulator by virtual screening and bioassays)[J].中国药理学报（英文版）,2022(09):2429-2438
A类：
atrophies,SGRMs,SGRM,transrepression
B类：
Discovery,novel,nonsteroidal,by,virtual,screening,bioassays,Synthetic,glucocorticoids,GCs,have,been,widely,treatment,broad,range,inflammatory,diseases,but,their,clinic,limited,undesired,side,effects,such,metabolic,disorders,osteoporosis,skin,muscle,mood,hypothalamic,pituitary,adrenal,HPA,axis,suppression,Selective,modulators,expected,promising,anti,efficacy,fewer,caused,Here,reported,HT,prospective,discovered,structure,VS,can,selectively,KB,AP1,mediated,function,expression,inflammation,cytokines,COX,CCL,effectively,dexamethasone,Dex,Compared,shows,less,transactivation,potency,that,associated,main,adverse,synthetic,cross,activities,other,nuclear,receptors,Furthermore,exhibits,weak,inhibition,ratio,OPG,RANKL,Therefore,may,reduce,induced,normal,bioactive,compound,serve,starting,point,development,therapeutics,high,dose,long,term
AB值：
0.584136
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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。
