Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases

作     者：Jiuping Zeng Mingxing Li Qianyun Zhao Meijuan Chen Long Zhao Shulin Wei Huan Yang Yueshui Zhao Anqi Wang Jing Shen Fukuan Du Yu Chen Shuai Deng Fang Wang Zhuo Zhang Zhi Li Tiangang Wang Shengpeng Wang Zhangang Xiao Xu Wu Jiuping Zeng;Mingxing Li;Qianyun Zhao;Meijuan Chen;Long Zhao;Shulin Wei;Huan Yang;Yueshui Zhao;Anqi Wang;Jing Shen;Fukuan Du;Yu Chen;Shuai Deng;Fang Wang;Zhuo Zhang;Zhi Li;Tiangang Wang;Shengpeng Wang;Zhangang Xiao;Xu Wu

作者机构：Laboratory of Molecular PharmacologyDepartment of PharmacologySchool of PharmacySouthwest Medical UniversityLuzhouSichuan646000China Cell Therapy&Cell Drugs of Luzhou Key LaboratoryLuzhouSichuan646000China South Sichuan Institute of Translational MedicineLuzhouSichuan646000China Department of Spleen and Stomach DiseasesThe Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhouSichuan646000China School of MedicineChengdu UniversityChengdu610106China State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical SciencesUniversity of MacaoMacao999078China Department of OncologyThe Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan646000China 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2023年第13卷第6期

页      面：545-562页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the grants from the Sichuan Science and Technology Program,China(Grant Nos.:2023NSFSC0614 and 2022YFS0624) Southwest Medical University Science and Technology Program,China(Grant No.:2021ZKZD017) the Luzhou Science and Technology Program,China(Grant Nos.:2022-YJY-127,2022YFS0624-B1,2022YFS0624-C1,and 2022YFS0624-B3) the Open Research Project Program funded by the Science and Technology Development Fund(Grant No.:SKL-QRCM(UM)-2020-2022) the State Key Laboratory of Quality Research in Chinese Medicine(University of Macao,Macao,China)(Grant No.:SKL-QRCMOP21006) 

主　　题：T helper 17 RORγt Small-molecule inhibitor Inflammatory disease Autoimmune disease 

摘      要：As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune *** emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 *** RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric-or allosteric-binding sites in the ligand-binding *** of small-molecule inhibitors have entered clinical ***,in current review,the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was ***,the recently developed RORγt inhibitors were summarized,with an emphasis on their optimization from lead compounds,efficacy,toxicity,mechanisms of action,and clinical *** limitations of current development in this area were also discussed to facilitate future research.