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Back Cover: Benzoxazepines Achieve Potent Suppression of IL‐17 Release in Human T‐Helper 17 (T H 17) Cells through an Induced‐Fit Binding Mode to the Nuclear Receptor RORγ (ChemMedChem 2/2016)
Author(s) -
Olsson Roine I.,
Xue Yafeng,
von Berg Stefan,
Aagaard Anna,
McPheat Jane,
Hansson Eva L.,
Bernström Jenny,
Hansson Pia,
Jirholt Johan,
Grindebacke Hanna,
Leffler Agnes,
Chen Rongfeng,
Xiong Yao,
Ge Hongbin,
Hansson Thomas G.,
Narjes Frank
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500605
Subject(s) - agonist , inverse agonist , chemistry , rar related orphan receptor gamma , stereochemistry , orphan receptor , benzamide , sulfonyl , receptor , retinoic acid receptor , retinoic acid , biochemistry , transcription factor , alkyl , organic chemistry , gene
The back cover picture shows structures of the retinoic acid‐related orphan receptor gamma (RORγ) with inverse agonist 15 [left, red; 2‐chloro‐6‐fluoro‐ N ‐(4‐{[3‐(trifluoromethyl)phenyl]sulfonyl}‐2,3,4,5‐tetrahydro‐1,4‐benzoxazepin‐7‐yl)benzamide)], and with agonist 25 [right, blue, ( N ‐(2‐fluorophenyl)‐4‐[(4‐fluorophenyl)sulfonyl]‐2,3,4,5‐tetrahydro‐1,4‐benzoxazepin‐6‐amine )]. Both an induced fit and an H‐bond to His 479 are necessary to disrupt the agonist conformation of the receptor, and it only takes minor structural changes to convert an inverse agonist into an agonist. These novel benzoxazepine‐based ligands for RORγ inhibit interleukin‐17 secretion with nanomolar potency. More information can be found in the Full Paper by Frank Narjes et al. on page 207 in Issue 2, 2016 (DOI: 10.1002/cmdc.201500432).