期刊
ACS CHEMICAL BIOLOGY
卷 11, 期 12, 页码 3442-3451出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.6b00677
关键词
-
资金
- Hauptman-Woodward Medical Research Institute
- U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]
PF-06651600, a newly discovered potent JAK3-selective inhibitor, is highly efficacious at inhibiting gamma c cytokine signaling, which is dependent on both JAK1 and JAK3. PF-06651600 allowed the comparison of JAK3-selective inhibition to pan-JAK or JAK1-selective inhibition, in relevant immune cells to a level that could not be achieved previously without such potency and selectivity. In vitro, PF-06651600 inhibits Th1 and Th17 cell differentiation and function, and in vivo it reduces disease pathology in rat adjuvant-induced arthritis as well as in mouse experimental autoimmune encephalomyelitis models. Importantly, by sparing JAK1 function, PF-06651600 selectively targets gamma c cytokine pathways while preserving JAK1-dependent antiinflammatory signaling such as the IL-10 suppressive functions following LPS treatment in macrophages and the suppression of TNF alpha and IL-1 beta production in IL-27-primed macrophages. Thus, JAK3-selective inhibition differentiates from pan-JAK or JAK1 inhibition in various immune cellular responses, which could potentially translate to advantageous clinical outcomes in inflammatory and autoimmune diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据