Engineering small‐molecule analogues of altiratinib via CREB‐regulated transcription co‐activator 3‐target screening for the development of potent and safe topical therapeutics against skin hyperpigmentary diseases.

This article discusses the development of topical therapeutics for the treatment of UV-induced skin hyperpigmentary disorders. The researchers used a screening tool to identify compounds that inhibit melanogenesis, the process of melanin synthesis. They engineered small-molecule analogues of a compound called altiratinib, which showed dose-dependent inhibitory action on melanogenesis but had cytotoxicity at higher concentrations. The researchers designed new compounds that demonstrated comparable or better efficacy in reducing melanin content without cytotoxicity. These compounds also showed enhanced skin permeability and were effective in reducing melanin content in mouse and human skin cultures. The findings suggest that these compounds have the potential to be developed into safe and potent topicals for the treatment of hyperpigmentary diseases. [Extracted from the article]