Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases
10.1016/j.jpha.2023.05.009
- Author:
Jiuping ZENG
1
,
2
;
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
Author Information
1. Laboratory of Molecular Pharmacology,Department of Pharmacology,School of Pharmacy,Southwest Medical University,Luzhou,Sichuan,646000,China
2. Cell Therapy & Cell Drugs of Luzhou Key Laboratory,Luzhou,Sichuan,646000,China
- Keywords:
T helper 17;
RORγt;
Small-molecule inhibitor;
Inflammatory disease;
Autoimmune disease
- From:
Journal of Pharmaceutical Analysis
2023;13(6):545-562
- CountryChina
- Language:Chinese
-
Abstract:
As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.
