Small molecular inhibitors targeting Janus kinases (JAKs) for the treatment of psoriasis

Psoriasis is a chronic inflammatory dermatological condition characterized by a complex pathogenesis involving the interplay of numerous cytokines and signaling pathways. Recently, Janus kinase (JAK) inhibitors have garnered considerable attention as a novel therapeutic approach due to their significant potential in modulating immune responses. By blocking the JAK signaling pathway, these inhibitors can reduce inflammation, offering promising potential for psoriasis treatment. Given the differences in selectivity, JAK inhibitors can be classified into three primary categories: first-generation, second-generation, and allosteric inhibitors targeting the pseudokinase domain. This review provides a comprehensive summary of the structure of JAKs and their role in the pathogenesis of psoriasis, in addition to highlighting recent advancements in the development of JAK inhibitors. It is expected that this perspective will facilitate the development of a new generation of JAK inhibitors with improved efficacy, increased selectivity, and reduced toxicity, thereby offering more optimal treatment regimens for patients with psoriasis.