Pharmacology of Janus kinase inhibitors

Modern dermatotherapy is dominated by the development of various biologicals and small molecules. Janus kinase inhibitors (JAKi) form a novel class of small molecular synthetic compounds inhibiting the intracellular signal transduction of cytokine receptors. Cytokines are key mediators in the pathophysiology of numerous inflammatory skin diseases. Many cytokines use so-called type I and II cytokine receptors, which associate with the Janus kinases JAK1, JAK2, JAK3 or TYK2. JAKi are under clinical investigation for inflammatory skin disease, specifically in phase 3 trials for psoriasis or atopic dermatitis. Since JAKi are tested in oral as well as in topical formulations, they could become very popular in dermatotherapy. The mechanisms of JAKi, their selectivity, preliminary efficacy data, and their safety profile are discussed in this article.