Poster presentation, P111

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Inhibition of Mitf-E box binding and its effect on pigmentation in Melan-a cell

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. To discover and evaluate the small molecule inhibitors of Mitf-E-box DNA, 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 assay, and Western blot were performed in melan-a cells. 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% with 25 uM). The results show that Compound #17 is the first small molecule inhibitor of Mitf-E-box DNA binding with depigmenting activity.

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