title: [Investigation of selective inhibition of digoxin derivative on retinoic acid-related orphan nuclear receptor γt transcription activity using molecular docking].
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Dhd can selectively suppress RORγt transcriptional activity.
authors.affiliation: Department of Dermatology and Venereology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.E-mail: zhongcaimei@aliyun.com.
authors.forename: Caimei
authors.initials: C
authors.lastname: Zhong
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Cai
authors.forename: Meirong
authors.initials: M
authors.lastname: Wang
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zheng
authors.forename: Xianwen
authors.initials: X
authors.lastname: Qiu
authors.forename: Ledong
authors.initials: L
authors.lastname: Sun
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Tangde
authors.initials: T
authors.lastname: Zhang
mesh_terms: D004077:Digoxin / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D008956:Models, Chemical; D062105:Molecular Docking Simulation; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; D004077:Digoxin