JANUS KINASE INHIBITORS IN DERMATOLOGY: PRESENT AND FUTURE

Abstract

New facts about the importance of the JAK−STAT signaling system in development of a number of inflammatory and autoimmune diseases are now emerging. The JAK−STAT system, or pathway consisting of Janus kinase (JAK) and signal transducer protein as well as transcription activator (STAT), transmits information from extracellular polypeptide signals through transmembrane receptors directly to target gene promoters in the nucleus without the involvement of secondary messengers. The JAK−STAT system plays an important role in the implementation of immunological processes and is considered a therapeutic target in immune−mediated inflammatory diseases. JAK inhibitors are so−called yakinibs, low molecular weight chemically synthesized targeted drugs that inhibit intracellular JAK signaling molecules and interrupt the effect of interleukins on the cell. Drugs have an acceptable benefit−risk ratio. The most common side effects are infections of the upper respiratory tract, urinary tract and gastrointestinal tract. The safety profile of topical JAK inhibitors is better than that of oral drugs due to their minimal systemic absorption. For the first time, JAK inhibitors have been shown to be effective in rheumatoid arthritis and myelofibrosis. Disordered regulation of the JAK−STAT signaling pathway is observed in various inflammatory and autoimmune skin diseases. JAK molecules are overexpressed in epidermis, dermis in psoriasis, atopic dermatitis, alopecia areata and vitiligo. Decoding the new mechanisms of pathogenesis of psoriasis, atopic dermatitis, alopecia areata, vitiligo created the preconditions for improving their pharmacotherapy with the use of inhibitors of Janus kinases. Today, JAK inhibitors are the most promising specific target agents when treating the immune−mediated dermatoses. Key words: JAK−STAT system, Janus kinase inhibitors, psoriasis, atopic dermatitis, alopecia areata, vitiligo.