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Selective inhibitors of the Janus kinase Jak3--Are they effective?

Gebhard Thoma1, Peter Drückes2, Hans-Günter Zerwes3

  • 1Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland.

Bioorganic & Medicinal Chemistry Letters
|September 14, 2014
PubMed

Jak3, together with Jak1, is involved in signal transduction initiated by cytokines signaling through the common gamma chain which are important in immune homeostasis and immune pathologies. Based on genetic evidence Jak3 has been considered to be an attractive target for immunosuppression. The Jak inhibitor tofacitinib (CP-690,550) which is an approved drug for rheumatoid arthritis was originally introduced as a selective Jak3 inhibitor, however, it also inhibits Jak1 and Jak2. The search for new selective Jak3 inhibitors has yielded several compounds whose profiles will be reviewed here. Implications on Jak3 as a therapeutic target are also discussed.

Keywords:
ImmunosuppressionJak1Jak3Janus kinase inhibitorsSelectivity

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