The small molecule ML233 is a direct inhibitor of tyrosinase function
Abstract Melanogenesis is the biological process regulating the synthesis of melanin pigments in melanocytes. Defective melanogenesis is associated with numerous human skin diseases, including, but not limited to, albinism, vitiligo, melasma, and hypo- and hyperpigmentation disorders. Tyrosinase is...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-03-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07973-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849392338258886656 |
|---|---|
| author | Romain Menard Aissette Baanannou Caroline Halluin Dexter Morse Sadie Kuhn Joel H. Graber James Strickland Romain Madelaine |
| author_facet | Romain Menard Aissette Baanannou Caroline Halluin Dexter Morse Sadie Kuhn Joel H. Graber James Strickland Romain Madelaine |
| author_sort | Romain Menard |
| collection | DOAJ |
| description | Abstract Melanogenesis is the biological process regulating the synthesis of melanin pigments in melanocytes. Defective melanogenesis is associated with numerous human skin diseases, including, but not limited to, albinism, vitiligo, melasma, and hypo- and hyperpigmentation disorders. Tyrosinase is the rate-limiting enzyme controlling melanogenesis, and hence tremendous efforts have been made to identify potent and safe inhibitors of tyrosinase function. However, despite decades of research, currently there is no effective treatment that inhibits melanogenesis or tyrosinase activity with no adverse side effects. In this study, we report the characterization of the ML233 chemical as a potent inhibitor of tyrosinase activity in vivo and in vitro. We demonstrate that ML233 reduces melanin production in the zebrafish model with no observable significant toxic side effects, and in murine melanoma cells. We also predict that these effects are mediated through direct tyrosinase-ML233 interaction, i.e., binding of the ML233 molecule to the active site of the protein to inhibit its function. Together, our results reveal that ML233 plays roles in both healthy and pathological skin cells via inhibition of melanin production. ML233-mediated tyrosinase inhibition is a potentially safe and effective approach to alleviate the symptoms of melanocyte-associated diseases and thereby substantially improve human health. |
| format | Article |
| id | doaj-art-bf51ecf891b8435692f01db785f2e12f |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-bf51ecf891b8435692f01db785f2e12f2025-08-20T03:40:47ZengNature PortfolioCommunications Biology2399-36422025-03-018111610.1038/s42003-025-07973-5The small molecule ML233 is a direct inhibitor of tyrosinase functionRomain Menard0Aissette Baanannou1Caroline Halluin2Dexter Morse3Sadie Kuhn4Joel H. Graber5James Strickland6Romain Madelaine7MDI Biological Laboratory, Kathryn W. Davis Center for Regenerative Biology and AgingMDI Biological Laboratory, Kathryn W. Davis Center for Regenerative Biology and AgingMDI Biological Laboratory, Kathryn W. Davis Center for Regenerative Biology and AgingMDI Biological Laboratory, Kathryn W. Davis Center for Regenerative Biology and AgingMDI BioscienceMDI Biological Laboratory, Kathryn W. Davis Center for Regenerative Biology and AgingMDI BioscienceMDI Biological Laboratory, Kathryn W. Davis Center for Regenerative Biology and AgingAbstract Melanogenesis is the biological process regulating the synthesis of melanin pigments in melanocytes. Defective melanogenesis is associated with numerous human skin diseases, including, but not limited to, albinism, vitiligo, melasma, and hypo- and hyperpigmentation disorders. Tyrosinase is the rate-limiting enzyme controlling melanogenesis, and hence tremendous efforts have been made to identify potent and safe inhibitors of tyrosinase function. However, despite decades of research, currently there is no effective treatment that inhibits melanogenesis or tyrosinase activity with no adverse side effects. In this study, we report the characterization of the ML233 chemical as a potent inhibitor of tyrosinase activity in vivo and in vitro. We demonstrate that ML233 reduces melanin production in the zebrafish model with no observable significant toxic side effects, and in murine melanoma cells. We also predict that these effects are mediated through direct tyrosinase-ML233 interaction, i.e., binding of the ML233 molecule to the active site of the protein to inhibit its function. Together, our results reveal that ML233 plays roles in both healthy and pathological skin cells via inhibition of melanin production. ML233-mediated tyrosinase inhibition is a potentially safe and effective approach to alleviate the symptoms of melanocyte-associated diseases and thereby substantially improve human health.https://doi.org/10.1038/s42003-025-07973-5 |
| spellingShingle | Romain Menard Aissette Baanannou Caroline Halluin Dexter Morse Sadie Kuhn Joel H. Graber James Strickland Romain Madelaine The small molecule ML233 is a direct inhibitor of tyrosinase function Communications Biology |
| title | The small molecule ML233 is a direct inhibitor of tyrosinase function |
| title_full | The small molecule ML233 is a direct inhibitor of tyrosinase function |
| title_fullStr | The small molecule ML233 is a direct inhibitor of tyrosinase function |
| title_full_unstemmed | The small molecule ML233 is a direct inhibitor of tyrosinase function |
| title_short | The small molecule ML233 is a direct inhibitor of tyrosinase function |
| title_sort | small molecule ml233 is a direct inhibitor of tyrosinase function |
| url | https://doi.org/10.1038/s42003-025-07973-5 |
| work_keys_str_mv | AT romainmenard thesmallmoleculeml233isadirectinhibitoroftyrosinasefunction AT aissettebaanannou thesmallmoleculeml233isadirectinhibitoroftyrosinasefunction AT carolinehalluin thesmallmoleculeml233isadirectinhibitoroftyrosinasefunction AT dextermorse thesmallmoleculeml233isadirectinhibitoroftyrosinasefunction AT sadiekuhn thesmallmoleculeml233isadirectinhibitoroftyrosinasefunction AT joelhgraber thesmallmoleculeml233isadirectinhibitoroftyrosinasefunction AT jamesstrickland thesmallmoleculeml233isadirectinhibitoroftyrosinasefunction AT romainmadelaine thesmallmoleculeml233isadirectinhibitoroftyrosinasefunction AT romainmenard smallmoleculeml233isadirectinhibitoroftyrosinasefunction AT aissettebaanannou smallmoleculeml233isadirectinhibitoroftyrosinasefunction AT carolinehalluin smallmoleculeml233isadirectinhibitoroftyrosinasefunction AT dextermorse smallmoleculeml233isadirectinhibitoroftyrosinasefunction AT sadiekuhn smallmoleculeml233isadirectinhibitoroftyrosinasefunction AT joelhgraber smallmoleculeml233isadirectinhibitoroftyrosinasefunction AT jamesstrickland smallmoleculeml233isadirectinhibitoroftyrosinasefunction AT romainmadelaine smallmoleculeml233isadirectinhibitoroftyrosinasefunction |