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bioRxiv · 10.1101/2024.02.14.580089

The p300 KAT inhibitor, A-485, inhibits melanogenesis and melanin content in human melanocytes

Grbic, N.·Waddell, A. R.·Leibowitz, K.·Wyant, W. A.·Collard, M.·Alani, R. M.
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Abstract

Hyperpigmentation disorders are commonly diagnosed dermatologic conditions that can be cosmetically distressing for patients and cause negative psychosocial impacts. There is a need to better understand the underlying pathophysiology of pigmentary disorders as well as develop improvements in the management of these disorders. Here, we evaluated a p300 (CBP/p300) histone acetyltransferase (HAT) inhibitor, A-485, to determine if epigenetically targeting melanogenesis could be of therapeutic value. We find that A-485 treatment of primary human melanocytes and SK-MEL-30 melanoma cells drastically reduces the mRNA and protein expression of MITF and DCT, genes involved in melanin synthesis, and that this is accompanied by a reduction in melanin content. These results suggest that epigenetically targeting melanin synthesis with the A-485 p300 HAT inhibitor may be beneficial for the treatment of hyperpigmentation disorders.

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Grbic, N., Waddell, A. R., Leibowitz, K., Wyant, W. A., Collard, M., Alani, R. M.. 2024-02-16. The p300 KAT inhibitor, A-485, inhibits melanogenesis and melanin content in human melanocytes. https://doi.org/10.1101/2024.02.14.580089

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