Abstract: Objetive Psoriasis 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. 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.