Discovery of small-molecule modulators of melanogenesis by docking-based virtual screening

Background: Vitiligo is a relatively common depigmenting skin disorder. UV light stimulation is often used to obtain repigmentation. Wnt signaling regulates melanocyte differentiation, and expression of TYR is upregulated in narrow-band UVB-treated epidermis. Manipulation of these two pathways by drugs could serve as one of the therapeutic approaches for durable repigmentation. Methods & results: CD9 was identified as a novel TYR activator by virtual screening and bioactivity assay. CD9 activated the Wnt signaling pathway through triggering translocation of β-catenin from cytoplasm to nucleus. Conclusion: The pathogenesis of vitiligo is complicated and varies with each individual, so combination therapy may be much more suitable for treatment of vitiligo. CD9 could synergize with other anti-inflammatory compounds or autoimmune suppressors to shorten repigmentation time and improve efficacy.