Investigation of selective inhibition of digoxin derivative on retinoic acid-related orphan nuclear receptor γt transcription activity using molecular docking.
- Author:
Caimei ZHONG
1
;
Yixuan CAI
;
Meirong WANG
;
Xiufen ZHENG
;
Xianwen QIU
;
Ledong SUN
;
Fan ZHANG
;
Tangde ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Digoxin; analogs & derivatives; pharmacology; Humans; Models, Chemical; Molecular Docking Simulation; Nuclear Receptor Subfamily 1, Group F, Member 1; antagonists & inhibitors; genetics; Transcription, Genetic
- From: Journal of Southern Medical University 2014;34(4):511-518
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVEPsoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptor γt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity.
METHODUsing molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORβ and RORγt), and the results were further confirmed by bioluminescent assay.
RESULTMolecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt; bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner.
CONCLUSIONDhd can selectively suppress RORγt transcriptional activity.
