A small molecule inhibitor of Mitf-E-box DNA binding and its depigmenting effect in melan-a cells

J. M. Um, H. J. Kim, Y. Lee, C. H. Choi, D. Hoang Nguyen, H. B. Lee, J. H. Shin, K. Tai No, E. K. Kim

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1291-1297
Number of pages7
JournalJournal of the European Academy of Dermatology and Venereology
Issue number10
Publication statusPublished - 2012 Oct

All Science Journal Classification (ASJC) codes

  • Dermatology
  • Infectious Diseases


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