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Discovery of betulinaldehyde as a natural ROR gamma t agonist

文献类型：期刊论文

作者Yang, Feng3,4; Zhang, Ruihan5; Ni, Dongxuan5; Luo, Xiaomin4; Chen, Shijie4; Luo, Cheng1,2,3,4; Xiao, Weilie5
刊名FITOTERAPIA
出版日期2019-09-01
卷号137页码:8
关键词ROR gamma t Receptor agonist Triterpenoids Alpha screen Molecular docking
ISSN号0367-326X
DOI10.1016/j.fitote.2019.104200
通讯作者Chen, Shijie(shijiechen@simm.ac.cn) ; Luo, Cheng(cluo@simm.ac.cn) ; Xiao, Weilie(xiaoweilie@ynu.edu.cn)
英文摘要Retinoic Acid Receptor-Related Orphan Receptor gamma t (ROR gamma t) is a dual-functional therapeutic target. The agonists and inhibitors of ROR gamma t are potential agents for tumor immunotherapy and autoimmune diseases, respectively, and sometimes share similar scaffolds. Although the widely distributed triterpenoid ursolic acid (UA) has been identified as a ROR gamma t inhibitor, the report of a triterpenoid ROR gamma t agonist is still absent. By screening an in-house triterpenoid library, we uncovered a novel ROR gamma t agonist, betulinaldehyde (1), together with an inhibitor (2, 3 beta, 28-Dihydroxy-lupan-29-oic acid). Compound 1 showed a good ROR gamma t activating effect with the EC50 of 11.4 mu M in Alpha Screen assay, and altered the thermal stability of ROR gamma t by directly binding to the protein in vitro. Combined with the SPR assay, the Kd value of compound 1 was examined as 2.99 mu M. The modulation mechanism of triterpenoid agonists and inhibitors were discussed by molecular docking. Herein, we firstly discovered compound 1 as a triterpenoid agonist of ROR gamma t. The co-distribution of triterpenoid ROR gamma t agonist and inhibitors in the same plant, might be related to the anti-inflammatory and anti-cancerous bioactivity of the plant extract.
WOS关键词CELLS ; DIFFERENTIATION ; DERIVATIVES ; LIGANDS ; PROGRAM
资助项目National Science and Technology Major Project[2018ZX09711002-004-013] ; National Science and Technology Major Project[2018ZX09711002-006-001] ; National Natural Science Foundation of China[81625022] ; National Natural Science Foundation of China[91853205] ; National Natural Science Foundation of China[81821005] ; National Natural Science Foundation of China[81703415] ; National Natural Science Foundation of China[21762048] ; K. C. Wong Education Foundation ; Shanghai Sailing Program[17YF1423100] ; Fudan-SIMM Joint Research Fund[FU-SIMM20174007] ; CAS Strategic Priority Research Program[XDA12020372] ; Yunnan Applicative and Basic Research Program[2018FY001] ; Yunnan Applicative and Basic Research Program[2018FA048] ; Program for Changjiang Scholoars and Innovative Research Team in University[IRT_17R94]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000484878400015
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/288676]  
专题新药研究国家重点实验室
通讯作者Chen, Shijie; Luo, Cheng; Xiao, Weilie
作者单位1.Guiyang Univ Tradit Chinese Med, Dept Pharm, South Dong Qing Rd, Guiyang 550025, Guizhou, Peoples R China
2.Fujian Med Univ, Dept Pharm, Fuzhou 350001, Fujian, Peoples R China
3.Fudan Univ, Sch Pharm, 826 Zhangheng Rd, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, CAS Key Lab Receptor Res,State Key Lab Drug Res, 555 Zu Chongzhi Rd, Shanghai 201203, Peoples R China
5.Yunnan Univ, Sch Chem Sci & Technol, Key Lab Med Chem Nat Resources, Minist Educ & Yunnan Prov, 2 Rd, Kunming 650091, Yunnan, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Feng,Zhang, Ruihan,Ni, Dongxuan,et al. Discovery of betulinaldehyde as a natural ROR gamma t agonist[J]. FITOTERAPIA,2019,137:8.
APA Yang, Feng.,Zhang, Ruihan.,Ni, Dongxuan.,Luo, Xiaomin.,Chen, Shijie.,...&Xiao, Weilie.(2019).Discovery of betulinaldehyde as a natural ROR gamma t agonist.FITOTERAPIA,137,8.
MLA Yang, Feng,et al."Discovery of betulinaldehyde as a natural ROR gamma t agonist".FITOTERAPIA 137(2019):8.

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来源：上海药物研究所

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