Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor
Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor
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DOI：
10.1126/science.1087061
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发表时间：
2003-10-31
期刊：
影响因子：
56.9
通讯作者：
Borie, DC
中科院分区：
文献类型：
--
作者：
Changelian, PS;Flanagan, ME;Borie, DC
由于其需要多种细胞因子的信号传导，Janus激酶3（JAK 3）是临床免疫抑制的极好靶点。我们报告了一种特异性的JAK 3口服活性抑制剂CP-690，550的开发，该抑制剂显著延长了心脏移植小鼠模型和接受肾移植的食蟹猴的存活时间。CP-690，550治疗与高血压、高脂血症或淋巴组织增生性疾病无关。基于这些临床前结果，我们认为CP-690，550阻断JAK 3在人体器官移植和其他临床环境中具有治疗上理想的免疫抑制潜力。
Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.