Literature DB >> 24900774

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

Ting Yang1, Qian Liu1, Yaobang Cheng1, Wei Cai1, Yingli Ma1, Liuqing Yang1, Qianqian Wu1, Lisa A Orband-Miller2, Ling Zhou1, Zhijun Xiang1, Melanie Huxdorf1, Wei Zhang1, Jing Zhang1, Jia-Ning Xiang1, Stewart Leung1, Yang Qiu1, Zhong Zhong1, John D Elliott1, Xichen Lin1, Yonghui Wang1.   

Abstract

A novel series of tertiary amines as retinoid-related orphan receptor gamma-t (RORγt) inverse agonists was discovered through agonist/inverse agonist conversion. The level of RORγt inhibition can be enhanced by modulating the conformational disruption of H12 in RORγt LBD. Linker exploration and rational design led to the discovery of more potent indole-based RORγt inverse agonists.

Entities:  

Keywords:  RORγt; Th17 cell differentiation; agonists; cocrystal structure; inverse agonists; structure-based design

Year:  2013        PMID： 24900774      PMCID： PMC4027777          DOI： 10.1021/ml4003875

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


  18 in total

1.  Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine.

Authors:  Ajay N Jain
Journal:  J Med Chem       Date:  2003-02-13       Impact factor: 7.446

2.  Parameter estimation for scoring protein-ligand interactions using negative training data.

Authors:  Tuan A Pham; Ajay N Jain
Journal:  J Med Chem       Date:  2006-10-05       Impact factor: 7.446

3.  Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORgamma.

Authors:  Lihua Jin; Dariusz Martynowski; Songyang Zheng; Taira Wada; Wen Xie; Yong Li
Journal:  Mol Endocrinol       Date:  2010-03-04

4.  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

5.  The VSGB 2.0 model: a next generation energy model for high resolution protein structure modeling.

Authors:  Jianing Li; Robert Abel; Kai Zhu; Yixiang Cao; Suwen Zhao; Richard A Friesner
Journal:  Proteins       Date:  2011-08-22

6.  Identification of Potent and Selective Diphenylpropanamide RORγ Inhibitors.

Authors:  Jun R Huh; Erika E Englund; Hang Wang; Ruili Huang; Pengxiang Huang; Fraydoon Rastinejad; James Inglese; Christopher P Austin; Ronald L Johnson; Wenwei Huang; Dan R Littman
Journal:  ACS Med Chem Lett       Date:  2013-01-10       Impact factor: 4.345

7.  The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen.

Authors:  A K Shiau; D Barstad; P M Loria; L Cheng; P J Kushner; D A Agard; G L Greene
Journal:  Cell       Date:  1998-12-23       Impact factor: 41.582

8.  Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity.

Authors:  Jun R Huh; Monica W L Leung; Pengxiang Huang; Daniel A Ryan; Michael R Krout; Raghu R V Malapaka; Jonathan Chow; Nicolas Manel; Maria Ciofani; Sangwon V Kim; Adolfo Cuesta; Fabio R Santori; Juan J Lafaille; H Eric Xu; David Y Gin; Fraydoon Rastinejad; Dan R Littman
Journal:  Nature       Date:  2011-03-27       Impact factor: 49.962

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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  19 in total

1.  SAR Exploration Guided by LE and Fsp(3): Discovery of a Selective and Orally Efficacious RORγ Inhibitor.

Authors:  Kazuyuki Hirata; Masayuki Kotoku; Noriyoshi Seki; Takaki Maeba; Katsuya Maeda; Shintaro Hirashima; Takayuki Sakai; Shingo Obika; Akimi Hori; Yasunori Hase; Takayuki Yamaguchi; Yoshiaki Katsuda; Takahiro Hata; Naoki Miyagawa; Kojo Arita; Yukihiro Nomura; Kota Asahina; Yusuke Aratsu; Masafumi Kamada; Tsuyoshi Adachi; Masato Noguchi; Satoki Doi; Paul Crowe; Erin Bradley; Ruo Steensma; Haiyan Tao; Morgan Fenn; Robert Babine; Xiaolin Li; Scott Thacher; Hiromasa Hashimoto; Makoto Shiozaki
Journal:  ACS Med Chem Lett       Date:  2015-11-04       Impact factor: 4.345

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

Review 3.  The dialogue between unconventional T cells and the microbiota.

Authors:  Qiaochu Lin; Meggie Kuypers; Dana J Philpott; Thierry Mallevaey
Journal:  Mucosal Immunol       Date:  2020-07-23       Impact factor: 7.313

4.  N-Arylsulfonyl Indolines as Retinoic Acid Receptor-Related Orphan Receptor γ (RORγ) Agonists.

Authors:  Christelle Doebelin; Rémi Patouret; Ruben D Garcia-Ordonez; Mi Ra Chang; Venkatasubramanian Dharmarajan; Dana S Kuruvilla; Scott J Novick; Li Lin; Michael D Cameron; Patrick R Griffin; Theodore M Kamenecka
Journal:  ChemMedChem       Date:  2016-11-23       Impact factor: 3.466

5.  A Residue-Resolved Bayesian Approach to Quantitative Interpretation of Hydrogen-Deuterium Exchange from Mass Spectrometry: Application to Characterizing Protein-Ligand Interactions.

Authors:  Daniel J Saltzberg; Howard B Broughton; Riccardo Pellarin; Michael J Chalmers; Alfonso Espada; Jeffrey A Dodge; Bruce D Pascal; Patrick R Griffin; Christine Humblet; Andrej Sali
Journal:  J Phys Chem B       Date:  2016-12-01       Impact factor: 2.991

6.  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

Review 7.  ROR nuclear receptors: structures, related diseases, and drug discovery.

Authors:  Yan Zhang; Xiao-yu Luo; Dong-hai Wu; Yong Xu
Journal:  Acta Pharmacol Sin       Date:  2014-12-15       Impact factor: 6.150

8.  From RORγt Agonist to Two Types of RORγt Inverse Agonists.

Authors:  Yonghui Wang; Wei Cai; Ting Tang; Qian Liu; Ting Yang; Liuqing Yang; Yingli Ma; Guifeng Zhang; Yafei Huang; Xiaoxia Song; Lisa A Orband-Miller; Qianqian Wu; Ling Zhou; Zhijun Xiang; Jia-Ning Xiang; Stewart Leung; Liming Shao; Xichen Lin; Mercedes Lobera; Feng Ren
Journal:  ACS Med Chem Lett       Date:  2018-01-22       Impact factor: 4.345

9.  Discovery and structural optimization of 4-(4-(benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-ones as RORc inverse agonists.

Authors:  Xi-Shan Wu; Rui Wang; Yan-Li Xing; Xiao-Qian Xue; Yan Zhang; Yong-Zhi Lu; Yu Song; Xiao-Yu Luo; Chun Wu; Yu-Lai Zhou; Jian-Qin Jiang; Yong Xu
Journal:  Acta Pharmacol Sin       Date:  2016-07-04       Impact factor: 6.150

Review 10.  (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
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