Delgocitinib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Delgocitinib (JTE-052, LEO 124249) 是一种有效的、选择性的、口服活性的泛 JAK 抑制剂，对 JAK1、2、3 和 Tyk2 的 IC50 分别为 2.8、2.6、13 和 58 nM。

Delgocitinib (JTE-052, LEO 124249) is a potent, selective, orally active, pan-JAK inhibitor with IC50 of 2.8, 2.6, 13 and 58 nM for JAK1,2,3 and Tyk2, respectively; does not inhibit a broad panel of kinases with exception of ROCK-II (IC50=140 nM); inhibits cytokine signaling evoked by IL-2, IL-6, IL-23, granulocyte/macrophage CSF, and IFN-α in vitro; potently suppresses the IL-2-induced IFN-γ production in mice (ED50=1.1 mg/kg), suppresses inflammatory responses in collagen-induced arthritis model.

In the enzymatic assays, Delgocitinib potently inhibits all of the 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 show that the inhibition mode of Delgocitinib toward all JAKs is competitive with ATP with Ki values of 2.1±0.3, 1.7±0.0, 5.5±0.3 and 14±1 nM for JAK1, JAK2, JAK3 and Tyk2, respectively.In these cell-based cytokine signaling assays, Delgocitinib inhibits the phosphorylation of Stat proteins 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, respectively. Delgocitinib also inhibits IL-2-induced proliferation of T cells in a concentration-dependent manner (IC50=8.9±3.6 nM), and its potency is similar to that of CP-690550 (IC50=16 nM).

Delgocitinib decreases the IFN-γ production, but the potency of the 1-h prior administration is higher than that of the 6-h prior administration (ED50=0.24 versus 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. Delgocitinib inhibits radiographic and histological changes of bone destruction and cartilage destruction. In the administration from day 15, Delgocitinib decreases the paw swelling in a dose-dependent manner. In addition, 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.

JTE052 | JTE-052 | LEO 124249 | LEO124249

Angiogenesis

JAK

JAK

Inflammation/Immunology

Psoriasis

1263774-59-9

310.361

C16H18N6O

>98% (HPLC)

DMSO : ≥ 58 mg/mL 186.89 mM

N#CCC(N1C[C@H](C)[C@]12CN(C3=C4C(NC=C4)=NC=N3)CC2)=O

3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)- 1,6-diazaspiro[3.4]octan-1-yl]-3-oxopropanenitrile

(-20℃)

With Ice Pack

≥ 2 years