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.
Artigo
em Chinês
| WPRIM (Pacífico Ocidental)
| ID: wpr-249418
Biblioteca responsável:
WPRO
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>
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Transcrição Gênica
/
Digoxina
/
Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares
/
Simulação de Acoplamento Molecular
/
Genética
/
Modelos Químicos
Tipo de estudo:
Estudo prognóstico
Limite:
Humanos
Idioma:
Chinês
Revista:
Journal of Southern Medical University
Ano de publicação:
2014
Tipo de documento:
Artigo