位置:首页 > 产品库 > Delgocitinib(JTE-052)
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
Delgocitinib(JTE-052)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Delgocitinib(JTE-052)图片
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)询价
1mg询价
5mg询价
10mg询价
25mg询价
50mg询价
100mg询价

Delgocitinib (JTE-052) (JTE-052) 是一种特异性 JAK 抑制剂,对 JAK1、JAK2、JAK3 和 Tyk2 的 IC50 分别为 2.8、2.6、13 和 58 nM。

Cell experiment:

in vitro experiments, Delgocitinib is dissolved in dimethyl sulfoxide (DMSO) and diluted with the buffer used in each experiment.--> For determination of IL-2-induced T cell proliferation, human T cells are precultured with 10 μg/mL PHA-M for 3 days and plated in 96-well plates at 1.0×104 cells/well in the presence or absence of various concentrations of Delgocitinib. Following preincubation with Delgocitinib for 30 min at 37℃, the cells are stimulated by adding 20 ng/mL recombinant human IL-2 to each well and incubated for 3 days at 37℃ under 5 % CO2. After completion of the culture period, the cells are harvested with a 96-well harvester and counted in a scintillation counter[1].

Animal experiment:

in vivo experiments, Delgocitinib is suspended in 0.5 % (w/v) methyl cellulose solution.--> Lewis rats are used in this study. First, collagen-induced arthritis (CIA) is induced in rats. Lewis rats are immunized with 1 mL of the emulsion (1 mg of type II collagen) via ten intradermal injections on the back under anesthesia. The rats are then challenged with 0.2 mL of the emulsion injected into the base of the tail on day 8 under anesthesia. Delgocitinib is given orally once daily from day 1 to day 21 (preventive administration) or from day 15 to day 28 (therapeutic administration). After arthritis induction, the hind paw volume is measured by a water displacement method using a plethysmometer. On day 22 or day 29, the rats are euthanized, and their hind paws are excised and X-rayed or processed for histological evaluation[1].

产品描述

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

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 tofacitinib (IC50=16 nM)[1].

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[1].

[1]. Tanimoto A, et al. Pharmacological properties of JTE-052: a novel potent JAK inhibitor that suppresses various inflammatory responses in vitro and in vivo. Inflamm Res. 2015 Jan;64(1):41-51.

 
 
维奥蛋白资源库 - 中文蛋白资源 CopyRight © 2010-2024