Alopecia areata (AA) is an immune-mediated condition that leads to non-scarring hair loss, affecting up to 2% of the global population1 and significantly deteriorates patients' quality of life and causes social withdrawal2.
Effective treatments for moderate to severe AA include Janus kinase (JAK) inhibitors1, which are first-line therapies targeting the immune pathways responsible for hair follicle destruction. By blocking JAK phosphorylation, these inhibitors prevent the activation of the JAK-STAT pathway and reduces inflammatory mediators. In particular, pan-JAK inhibitors provide a broad mechanism of action by modulating cytokine signaling pathways involved3. They have demonstrated efficacy in conditions such as alopecia areata, atopic dermatitis, vitiligo, and psoriasis.
While small molecule JAK inhibitors have shown success, there is a need for peptide-based alternatives. Peptide drugs offer advantages4, including enhanced target specificity, potency, reduced side effects, and customizable structures.
Our research aims to develop a one-bead-one-compound (OBOC) peptide library5 to explore this avenue. We have created a peptide library consisting of 10^7 peptides using the split-and-pool method. This library will be screened against JAK 1-3 using a magnetic screening strategy. Peptide sequencing will follow via tandem mass spectrometry, with lead sequences undergoing alanine scanning and optimization. Finally, promising candidates will be conjugated with cell- or dermis-penetrating peptides and tested in vitro and in vivo.
In conclusion, this project aims to broaden the therapeutic landscape for alopecia areata by developing innovative peptide-based pan-JAK inhibitors and exploring their potential applications in other treatments.