Delgocitinib 是一种特异性JAK抑制剂，对 JAK1、JAK2、JAK3 和 Tyk2 的IC50值分别为 2.8、2.6、13 和 58 nM。

Delgocitinib is a novel and specific inhibitor of JAK (IC50s: 2.8, 2.6, 13 and 58 nM for JAK1, JAK2, JAK3 and Tyk2, respectively) .

Delgocitinib inhibits the phosphorylation of Stat proteins induced by IL-2, IL-6, IL-23, GM-CSF, and IFN-α (IC50: 40±9, 33±14, 84±11, 304±22 and 18±3 nM, respectively), in these cell-based cytokine signaling assays and it also inhibits IL-2-induced proliferation of T cells in a concentration-dependent manner (IC50: 8.9±3.6 nM). Its potency is similar to that of tofacitinib (IC50:16 nM). Delgocitinib effectively inhibits all of the JAK subtypes ( IC50: 2.8±0.6, 2.6±0.2, 13±0 and 58±9 nM for JAK1, JAK2, JAK3 and Tyk2, respectively), in the enzymatic assays. 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 inhibits radiographic and histological changes of bone destruction and cartilage destruction. Delgocitinib induces the IFN-γ production, however, the potency of the 1-h prior administration(ED50: 0.24 mg/kg) is higher than that of the 6-h prior administration (ED50: 1.3 mg/kg). In the administration from day 1, Delgocitinib prevents the development of hind paw swelling and histological changes of inflammatory cell infiltration and synovial cell hyperplasia. In the administration from day 15, Delgocitinib decreases the paw swelling in a dose-dependent manner. Delgocitinib ameliorates the inflammatory cell infiltration, synovial cell hyperplasia, and cartilage/bone destructions in the histological and radiographic examinations at the end of the study[1].

1263774-59-9

C16H18N6O

310.35

迪高替尼;JTE-052;Corectim（Delgocitinib）

DMSO:50 mg/mL (161.11 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years