Literature DB >> 29456799

From RORγt Agonist to Two Types of RORγt Inverse Agonists.

Yonghui Wang1, Wei Cai2, Ting Tang1, Qian Liu2, Ting Yang2, Liuqing Yang2, Yingli Ma2, Guifeng Zhang2, Yafei Huang1, Xiaoxia Song1, Lisa A Orband-Miller2, Qianqian Wu2, Ling Zhou2, Zhijun Xiang2, Jia-Ning Xiang2, Stewart Leung2, Liming Shao1, Xichen Lin2, Mercedes Lobera3, Feng Ren2.   

Abstract

Biaryl amides as new RORγt modulators were discovered. The crystal structure of biaryl amide agonist 6 in complex with RORγt ligand binding domain (LBD) was resolved, and both "short" and "long" inverse agonists were obtained by removing from 6 or adding to 6 a proper structural moiety. While "short" inverse agonist (8) recruits a corepressor peptide and dispels a coactivator peptide, "long" inverse agonist (9) dispels both. The two types of inverse agonists can be utilized as potential tools to study mechanisms of Th17 transcriptional network inhibition and related disease biology.

Entities:  

Year:  2018        PMID： 29456799      PMCID： PMC5807863          DOI： 10.1021/acsmedchemlett.7b00476

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  26 in total

1.  Discovery of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as potent RORγt inverse agonists.

Authors:  Yonghui Wang; Ting Yang; Qian Liu; Yingli Ma; Liuqing Yang; Ling Zhou; Zhijun Xiang; Ziqiang Cheng; Sijie Lu; Lisa A Orband-Miller; Wei Zhang; Qianqian Wu; Kathleen Zhang; Yi Li; Jia-Ning Xiang; John D Elliott; Stewart Leung; Feng Ren; Xichen Lin
Journal:  Bioorg Med Chem       Date:  2015-08-01       Impact factor: 3.641

2.  Minor Structural Change to Tertiary Sulfonamide RORc Ligands Led to Opposite Mechanisms of Action.

Authors:  Olivier René; Benjamin P Fauber; Gladys de Leon Boenig; Brenda Burton; Céline Eidenschenk; Christine Everett; Alberto Gobbi; Sarah G Hymowitz; Adam R Johnson; James R Kiefer; Marya Liimatta; Peter Lockey; Maxine Norman; Wenjun Ouyang; Heidi A Wallweber; Harvey Wong
Journal:  ACS Med Chem Lett       Date:  2014-12-04       Impact factor: 4.345

3.  Ursolic acid suppresses interleukin-17 (IL-17) production by selectively antagonizing the function of RORgamma t protein.

Authors:  Tao Xu; Xiaohu Wang; Bo Zhong; Roza I Nurieva; Sheng Ding; Chen Dong
Journal:  J Biol Chem       Date:  2011-05-12       Impact factor: 5.157

4.  The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells.

Authors:  Ivaylo I Ivanov; Brent S McKenzie; Liang Zhou; Carlos E Tadokoro; Alice Lepelley; Juan J Lafaille; Daniel J Cua; Dan R Littman
Journal:  Cell       Date:  2006-09-22       Impact factor: 41.582

5.  Discovery of Tertiary Amine and Indole Derivatives as Potent RORγt Inverse Agonists.

Authors:  Ting Yang; Qian Liu; Yaobang Cheng; Wei Cai; Yingli Ma; Liuqing Yang; Qianqian Wu; Lisa A Orband-Miller; Ling Zhou; Zhijun Xiang; Melanie Huxdorf; Wei Zhang; Jing Zhang; Jia-Ning Xiang; Stewart Leung; Yang Qiu; Zhong Zhong; John D Elliott; Xichen Lin; Yonghui Wang
Journal:  ACS Med Chem Lett       Date:  2013-11-22       Impact factor: 4.345

Review 6.  Inhibiting RORγt/Th17 axis for autoimmune disorders.

Authors:  Fujio Isono; Saori Fujita-Sato; Shuichiro Ito
Journal:  Drug Discov Today       Date:  2014-04-30       Impact factor: 7.851

Review 7.  Targeting Th17 cells in autoimmune diseases.

Authors:  Jianfei Yang; Mark S Sundrud; Jill Skepner; Tetsuya Yamagata
Journal:  Trends Pharmacol Sci       Date:  2014-08-14       Impact factor: 14.819

Review 8.  Action of RORs and their ligands in (patho)physiology.

Authors:  Laura A Solt; Thomas P Burris
Journal:  Trends Endocrinol Metab       Date:  2012-07-11       Impact factor: 12.015

9.  Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand.

Authors:  Laura A Solt; Naresh Kumar; Philippe Nuhant; Yongjun Wang; Janelle L Lauer; Jin Liu; Monica A Istrate; Theodore M Kamenecka; William R Roush; Dušica Vidović; Stephan C Schürer; Jihong Xu; Gail Wagoner; Paul D Drew; Patrick R Griffin; Thomas P Burris
Journal:  Nature       Date:  2011-04-17       Impact factor: 49.962

Review 10.  Small molecule inhibitors of RORγt: targeting Th17 cells and other applications.

Authors:  Jun R Huh; Dan R Littman
Journal:  Eur J Immunol       Date:  2012-09       Impact factor: 5.532
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  5 in total

1.  Molecular dynamics simulations on RORγt: insights into its functional agonism and inverse agonism.

Authors:  Cong-Min Yuan; Hai-Hong Chen; Nan-Nan Sun; Xiao-Jun Ma; Jun Xu; Wei Fu
Journal:  Acta Pharmacol Sin       Date:  2019-07-17       Impact factor: 6.150

2.  Statistical Analysis of Protein-Ligand Interaction Patterns in Nuclear Receptor RORγ.

Authors:  Bill Pham; Ziju Cheng; Daniel Lopez; Richard J Lindsay; David Foutch; Rily T Majors; Tongye Shen
Journal:  Front Mol Biosci       Date:  2022-06-15

3.  Crystallography-guided discovery of carbazole-based retinoic acid-related orphan receptor gamma-t (RORγt) modulators: insights into different protein behaviors with "short" and "long" inverse agonists.

Authors:  Ming-Cheng Yu; Feng Yang; Xiao-Yu Ding; Nan-Nan Sun; Zheng-Yuan Jiang; Ya-Fei Huang; Yu-Rong Yan; Chen Zhu; Qiong Xie; Zhi-Feng Chen; Si-Qi Guo; Hua-Liang Jiang; Kai-Xian Chen; Cheng Luo; Xiao-Min Luo; Shi-Jie Chen; Yong-Hui Wang
Journal:  Acta Pharmacol Sin       Date:  2020-11-25       Impact factor: 7.169

Review 4.  (Inverse) Agonists of Retinoic Acid-Related Orphan Receptor γ: Regulation of Immune Responses, Inflammation, and Autoimmune Disease.

Authors:  Anton M Jetten; Donald N Cook
Journal:  Annu Rev Pharmacol Toxicol       Date:  2019-08-06       Impact factor: 13.820

5.  Molecular Mechanism of Action of RORγt Agonists and Inverse Agonists: Insights from Molecular Dynamics Simulation.

Authors:  Nannan Sun; Congmin Yuan; Xiaojun Ma; Yonghui Wang; Xianfeng Gu; Wei Fu
Journal:  Molecules       Date:  2018-12-03       Impact factor: 4.411
  5 in total

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