High-throughput screening of small molecule Wnt/β-catenin activators for hair and nail growth

Hair and nails, though structurally different, both rely on Wnt/β-catenin signaling for regeneration. To identify small molecules that enhance this pathway, we screened 5,170 FDA-approved and natural compounds using HEK293 cells with a TCF/LEF luciferase reporter. Nine compounds significantly activated Wnt signaling, including antivirals (imidocarb, proflavine, aminoacridine), anticancer agents (entinostat, enzastaurin, abemaciclib), and GSK-3β inhibitors (BIO, CP21R7). Aminoacridine and proflavine markedly upregulated RSPO3 and RSPO4 while suppressing WIF1. In mice, aminoacridine-especially combined with minoxidil-showed the strongest hair regrowth, while proflavine and imidocarb enhanced nail elongation. These results reveal new therapeutic candidates for hair and nail regeneration.