Investigation of selective inhibition of digoxin derivative on retinoic acid-related orphan nuclear receptor γt transcription activity using molecular docking / 南方医科大学学报
Journal of Southern Medical University
;
(12): 511-518, 2014.
Article
Dans Chinois
| WPRIM
| ID: wpr-249418
ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>Dhd can selectively suppress RORγt transcriptional activity.</p>
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Pharmacologie
/
Transcription génétique
/
Digoxine
/
Membre-1 du groupe F de la sous-famille-1 de récepteurs nucléaires
/
Simulation de docking moléculaire
/
Génétique
/
Modèles chimiques
Type d'étude:
Étude pronostique
Limites du sujet:
Humains
langue:
Chinois
Texte intégral:
Journal of Southern Medical University
Année:
2014
Type:
Article
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