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

Future Med Chem. 2022 Feb;14(4):221-231. doi: 10.4155/fmc-2021-0150. Epub 2021 Dec 23.

Abstract

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.

Keywords: TYR; Wnt signaling; combination therapy; melanogenesis; vitiligo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • Ligands
  • Melanins / metabolism*
  • Mice
  • Molecular Docking Simulation*
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / metabolism
  • Small Molecule Libraries / pharmacology
  • Small Molecule Libraries / therapeutic use
  • Tetraspanin 29 / chemistry
  • Tetraspanin 29 / metabolism
  • Vitiligo / drug therapy
  • Wnt Signaling Pathway / drug effects

Substances

  • Ligands
  • Melanins
  • Small Molecule Libraries
  • Tetraspanin 29