Investigation of selective inhibition of digoxin derivative on retinoic acid-related orphan nuclear receptorγt transcription activity using molecular docking
ZHONG Caimei
CAI Yixuan
WANG Meirong
ZHENG Xiufen
QIU Xianwen
SUN Ledong
ZHANG Fan
ZHANG Tangde
Abstract：Objetive Psoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptorγt (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. Method Using 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. Result Molecular 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. Conclusion Dhd can selectively suppress RORγt transcriptional activity.
Keywords：RORγtmolecular dockingdigoxinimmune diease
Publication Date：2014-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：8( 511-518 )