Delgocitinib (JTE-052) is a specific JAK (Janus kinase) inhibitor with IC50 values of 2.8, 2.6, 13, and 58 nM for JAK1, JAK2, JAK3, and Tyk2 respectively. Delgocitinib is involved in various inflammatory and autoimmune diseases through JAK-dependent cytokines and can effectively suppress multiple cytokine signaling while inhibiting itching caused by cytokines. It is widely used to treat various inflammatory diseases, including autoimmune diseases and hypersensitivity reactions.

JAK3:13 nM, JAK2:2.6 nM, JAK1:2.8 nM, TYK2:58 nM

In cytokine signaling assays, Delgocitinib demonstrates inhibition of Stat protein phosphorylation induced by IL-2, IL-6, IL-23, GM-CSF, and IFN-α, with IC50 values of 40±9, 33±14, 84±11, 304±22, and 18±3 nM. It concentration-dependently suppresses IL-2-induced T cell proliferation (IC50: 8.9±3.6 nM), exhibiting a potency comparable to Tofacitinib (IC50: 16 nM). In the enzymatic assays, Delgocitinib effective inhibition of all JAK subtypes, with IC50 values of 2.8±0.6, 2.6±0.2, 13±0, and 58±9 nM for JAK1, JAK2, JAK3, and Tyk2, respectively. Lineweaver-Burk plots display that the inhibition mode of Delgocitinib toward all JAKs is competitive with ATP (Ki: 2.1±0.3, 1.7±0.0, 5.5±0.3 and 14±1 nM for JAK1, JAK2, JAK3 and Tyk2, respectively) [1].

Delgocitinib (oral; mice) effectively suppresses inflammatory responses. Orally administered Delgocitinib 1 or 6 hours before IL-2 injection, Delgocitinib can reduce the production of IFN-γ, but the efficacy of administration in the first 1 hour is higher than that of administration in the first 6 hours (ED50 = 0.24 vs. 1.3 mg/kg). Delgocitinib (oral; 0.1, 1, or 10 mg/kg; mouse) ameliorates rat collagen-induced arthritis model. Delgocitinib prevented the development of hind paw swelling and histological changes in inflammatory cell infiltration and synoviocyte proliferation before the onset of rat collagen-induced arthritis (administration starting on day 1). Delgocitinib reduced paw swelling in a dose-dependent manner after the onset of rat collagen-induced arthritis (administration starting on day 15), with improvement in paw swelling noted as early as the second day after administration. These findings suggest that Delgocitinib has a protective effect against joint inflammation and joint destruction [1].