Tyk2 Inhibitors

Tyk2 Inhibitors – Target Pipeline List 04/2019

Targets: Non-receptor tyrosine-protein kinase 2; Tyk2

This Target Pipeline List provides an overview of small molecule inhibitors of Tyk2 in development for treatment of inflammatory diseases.

Non-receptor tyrosine-protein kinase 2 (TYK2) is an enzyme that in humans is encoded by the TYK2 gene. Tyk2 was the first member of the janus kinase (JAK) family that was described (the other members are JAK1, JAK2, and JAK3).

TYK2, an intracellular signaling kinase, mediates cytokine-driven immune and pro-inflammatory signaling pathways that are critical in the cycle of chronic inflammation central to immune-mediated diseases. TYK2 mediates signaling of IL-23, IL-12, and Type I IFN-driven responses but not cytokine responses mediated by other kinases, such as IL-6, hematopoietic growth factors and the IL-2 family. TYK2 signaling is implicated in the pathophysiology of various immune-mediated diseases including psoriasis, lupus and inflammatory bowel disease.

The pipeline of Tyk2 inhibitors includes Tyk2-selective small molecules as well as dual Jak1/Tyk2 specific inhibitors and some multi-targeted Tyk2 inhibitors. The most advanced Tyk2 inhibitor currently is being evaluated in a phase III program in psoriasis. Other indications for which selective Tyk2 and dual Jak1/Tyk2 inibitors are being studied, include systemic lupus erythematosus, ulcerative colitis, Crohn’s disease, psoriatic arthritis, non-infectious uveitis, atopic dermatitis, alopecia areata and vitiligo.

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