CS12192 Reverses Alopecia Areata by Selectively Targeting JAK3/JAK1/TBK1

The study investigates the efficacy and safety of CS12192, a selective JAK3 inhibitor that also partially inhibits JAK1 and TBK1, in treating alopecia areata (AA) using a C3H/HeJ skin-transplanted AA mouse model. CS12192 demonstrated a dose-dependent ability to reverse hair growth inhibition, with high doses showing effectiveness comparable to baricitinib but with improved safety. Both CS12192 and baricitinib significantly reduced immune cell infiltration, particularly CD8+ T cells, in the skin of AA mice. Mechanistic analysis using CyTOF and RNA-seq revealed similarities in how both compounds regulate AA-related immune cells and signaling pathways. CS12192 shows promise as a novel treatment for AA with potentially better safety profiles.