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

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.