您好,欢迎来到试剂信息网! [登录] [免费注册]
试剂信息网
位置:首页 > 产品库 > PF-06651600
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:
 
PF-06651600
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。
PF-06651600图片
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议

产品介绍
PF-06651600 (PF-06651600) 是一种具有口服活性的选择性 JAK3 抑制剂,IC50 为 33.1 nM。

Cell experiment:

To study the effect of PF-06651600 on Th17 cells post differentiation, skewed Th17 cells are washed, rested with medium for overnight and resuspended in medium containing the same concentrations of cytokines as during skewing but without anti-CD3 or anti-CD28 antibodies, in the presence of PF-06651600 at 10 different concentrations for 2 additional days. On Day 9, supernatant is harvested from each well and IL-17A is determined[1].

Animal experiment:

The effect of JAK3 inhibition by PF-06651600 is evaluated in vivo using a therapeutic dosing paradigm in a rat adjuvant-induced arthritis. When individual hind paw volume measurements indicate an increase of 0.2 mL (or greater) in a single hind paw, animals are randomly assigned to a treatment group. Daily treatment with PF-06651600 is administered via oral gavage. Treatment groups for Experiment 1 are: 80, 15, or 6 mg/kg of PF-06651600 or vehicle (2% Tween 80/0.5% methylcellulose/deionized water). Treatment groups for Experiment 2 are: 30, 10, and 3 mg/kg of PF-06651600 or vehicle (0.5% methylcellulose/de-ionized water/1 mEQ hydrochloric acid). Treatment groups for Experiment 3 are: 10, 1, 0.3 and 0.1 mg/kg of PF-06651600 or vehicle (0.5% methylcellulose/de-ionized water/1 mEQ hydrochloric acid). Treatment continues for 7 days[1].

产品描述

PF-06651600 is a potent JAK3-selective inhibitor with an IC50 of 33.1 nM.

PF-06651600 is a potent JAK3-selective inhibitor which can inhibit the JAK3 kinase activity with an IC50 of 33.1 nM but without activity (IC50>10.000 nM) against JAK1, JAK2, and TYK2. PF-06651600 inhibits the phosphorylation of STAT5 elicited by IL-2, IL-4, IL-7, and IL-15 with IC50 values of 244, 340, 407, and 266 nM, respectively. PF-06651600 also inhibits the phosphorylation of STAT3 elicited by IL-21 with an IC50 of 355 nM. Functional assessment in T-cell differentiation assays demonstrate that PF-06651600 suppresses Th1 and Th17 differentiation as measured by IFNγ, after 5 days under Th1 conditions, and IL-17 production, after 6 days under Th17 conditions, with IC50 values of 30 nM and 167 nM, respectively. PF-06651600 also suppresses Th1 and Th17 function as measured by the inhibition of IFNγ production (IC50=48 nM) and IL-17 production (IC50=269 nM) in cells that have been previously differentiated and rested before being treated with PF-06651600[1].

In the rat adjuvant-induced arthritis (AIA) model, PF-06651600 reduces paw swelling with an unbound EC50 of 169 nM. Similarly, PF-06651600 significantly reduces disease severity in the experimental autoimmune encephalomyelitis (EAE) mouse model when dosed either therapeutically at 30 or 100 mg/kg or prophylactically at 20 and 60 mg/kg. The efficacy of PF-06651600 in these two rodent models of inflammatory and autoimmune diseases illustrates that JAK3-selective inhibition can be sufficient to have disease modifying effects in human diseases[1].

References:
[1]. Telliez JB, et al. Discovery of a JAK3-Selective Inhibitor: Functional Differentiation of JAK3-Selective Inhibition over pan-JAK or JAK1-Selective Inhibition. ACS Chem Biol. 2016 Dec 16;11(12):3442-3451.