title: A small molecule inhibitor of Mitf-E-box DNA binding and its depigmenting effect in melan-a cells.
abstract: BACKGROUND
  Microphthalmia associated transcription factor (Mitf) is a key regulatory transcriptional factor of pigmentation-related genes including tyrosinase. Inhibition of tyrosinase transcription by blocking the binding of Mitf with its promoter E-box DNA can control the pigmentation. However, no such chemicals were reported so far.
  
  
  OBJECTIVE
  To discover and evaluate the small molecule inhibitors of Mitf-E-box DNA.
  
  
  METHODS
  Candidate chemicals were screened by virtual screening from pharmacophore data followed by Mitf E-box DNA protein chip. After selecting the chemical, its inhibitory activity on binding interaction between Mitf and E-box DNA, electrophoretic mobility shift assay (EMSA) was performed. To evaluate the depigmenting activity of Compound #17, cellular melanin assa, and Western blot were performed in melan-a cells.
  
  
  RESULTS
  Among 27 chemicals selected from a pharmacophore data by virtual screening, Compound #17 was screened, which showed the most potent inhibitory activity against Mitf-E-box DNA binding in protein chip. EMSA results confirmed the specific inhibition of Compound #17 on Mitf-E-box DNA binding. In melan-a cells, Compound #17 reduced tyrosinase expression and melanin synthesis (62.5% at 25 μM).
  
  
  CONCLUSIONS
  The results show that Compound #17 is the first small molecule inhibitor of Mitf-E-box DNA binding with depigmenting activity.
authors.affiliation: Department of Biological Engineering, National Lab of Skin-bioactive Material, Inha University Department of Dermatology, College of Medicine, Inha University, Incheon, Korea.
authors.forename: J-M
authors.initials: JM
authors.lastname: Um
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: Y
authors.initials: Y
authors.lastname: Lee
authors.forename: C-H
authors.initials: CH
authors.lastname: Choi
authors.forename: D
authors.initials: D
authors.lastname: Hoang Nguyen
authors.forename: H-B
authors.initials: HB
authors.lastname: Lee
authors.forename: J-H
authors.initials: JH
authors.lastname: Shin
authors.forename: K
authors.initials: K
authors.lastname: Tai No
authors.forename: E-K
authors.initials: EK
authors.lastname: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002461:Cell Line, Transformed; D004247:DNA / Q000378:metabolism*; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D054852:Small Molecule Libraries
chemical_list: D017931:DNA Primers; D051739:Microphthalmia-Associated Transcription Factor; D054852:Small Molecule Libraries; D004247:DNA