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, Kyoung Tai No, E. K. Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1291-1297
Number of pages7
JournalJournal of the European Academy of Dermatology and Venereology
Volume26
Issue number10
DOIs
Publication statusPublished - 2012 Oct 1

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Microphthalmia-Associated Transcription Factor
DNA
Monophenol Monooxygenase
Protein Array Analysis
Melanins
Pigmentation
Electrophoretic Mobility Shift Assay
DNA-Binding Proteins
Oligonucleotide Array Sequence Analysis
Western Blotting
compound 17

All Science Journal Classification (ASJC) codes

  • Dermatology
  • Infectious Diseases

Cite this

Um, J. M. ; Kim, H. J. ; Lee, Y. ; Choi, C. H. ; Hoang Nguyen, D. ; Lee, H. B. ; Shin, J. H. ; No, Kyoung Tai ; Kim, E. K. / A small molecule inhibitor of Mitf-E-box DNA binding and its depigmenting effect in melan-a cells. In: Journal of the European Academy of Dermatology and Venereology. 2012 ; Vol. 26, No. 10. pp. 1291-1297.
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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.",
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A small molecule inhibitor of Mitf-E-box DNA binding and its depigmenting effect in melan-a cells. / Um, J. M.; Kim, H. J.; Lee, Y.; Choi, C. H.; Hoang Nguyen, D.; Lee, H. B.; Shin, J. H.; No, Kyoung Tai; Kim, E. K.

In: Journal of the European Academy of Dermatology and Venereology, Vol. 26, No. 10, 01.10.2012, p. 1291-1297.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Um, J. M.

AU - Kim, H. J.

AU - Lee, Y.

AU - Choi, C. H.

AU - Hoang Nguyen, D.

AU - Lee, H. B.

AU - Shin, J. H.

AU - No, Kyoung Tai

AU - Kim, E. K.

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N2 - 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.

AB - 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.

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