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Pharmakologie der Januskinaseinhibitoren

Pharmacology of Janus kinase inhibitors

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Zusammenfassung

Die moderne Dermatotherapie wird von der Entwicklung von zahlreichen Biologika, aber auch von kleinen Molekülen dominiert. Januskinaseinhibitoren (JAKi) bilden eine neue Substanzklasse niedermolekularer chemisch synthetisierter Pharmaka, die die intrazelluläre Signaltransduktion von Zytokinrezeptoren hemmen. Zytokine sind in der Pathophysiologie unterschiedlichster Hautkrankheiten von Bedeutung. Viele Zytokine verwenden sog. Typ-I- und -II-Zytokinrezeptoren, die mit den Januskinasen(JAK)1, JAK2, JAK3 oder TYK(Tyrosinkinase)2 interagieren. JAKi befinden sich für entzündliche Hautkrankheiten wie Psoriasis oder atopisches Ekzem bereits in der klinischen Phase-3-Prüfung. Da sie sowohl in oraler als auch in topischer Formulation untersucht werden, könnten sie gerade in der Dermatotherapie schnell Einzug halten. Die Mechanismen von JAKi, ihre Selektivität, erste Wirksamkeitsdaten und ihr Sicherheitsprofil werden in diesem Beitrag diskutiert.

Abstract

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.

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Authors and Affiliations

  1. Klinik für Dermatologie, Venerologie und Allergologie, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland

    F. Solimani, F. J. Hilke &  K. Ghoreschi M.D.

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  1. F. Solimani
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  2. F. J. Hilke
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  3. K. Ghoreschi M.D.
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Correspondence to K. Ghoreschi M.D..

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Interessenkonflikt

K. Ghoreschi hat Honorare oder Reisekosten für Vortrags- und Forschungsaktivitäten von AbbVie, Almirall, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Delenex, Eli Lilly, Galderma, Janssen-Cilag, Medac, MSD, Novartis, Pfizer und UCB Pharma erhalten. F. Solimani und F.J. Hilke geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Solimani, F., Hilke, F.J. & Ghoreschi, K. Pharmakologie der Januskinaseinhibitoren. Hautarzt 70, 934–941 (2019). https://doi.org/10.1007/s00105-019-04509-x

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