一种特异性Janus激酶3抑制剂对器官同种异体移植排斥反应的预防作用
Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor.
作者信息
Changelian Paul S, Flanagan Mark E, Ball Douglas J, Kent Craig R, Magnuson Kelly S, Martin William H, Rizzuti Bonnie J, Sawyer Perry S, Perry Bret D, Brissette William H, McCurdy Sandra P, Kudlacz Elizabeth M, Conklyn Maryrose J, Elliott Eileen A, Koslov Erika R, Fisher Michael B, Strelevitz Timothy J, Yoon Kwansik, Whipple David A, Sun Jianmin, Munchhof Michael J, Doty John L, Casavant Jeffrey M, Blumenkopf Todd A, Hines Michael, Brown Matthew F, Lillie Brett M, Subramanyam Chakrapani, Shang-Poa Chang, Milici Anthony J, Beckius Gretchen E, Moyer James D, Su Chunyan, Woodworth Thasia G, Gaweco Anderson S, Beals Chan R, Littman Bruce H, Fisher Douglas A, Smith James F, Zagouras Panayiotis, Magna Holly A, Saltarelli Mary J, Johnson Kimberly S, Nelms Linda F, Des Etages Shelley G, Hayes Lisa S, Kawabata Thomas T, Finco-Kent Deborah, Baker Deanna L, Larson Michael, Si Ming-Sing, Paniagua Ricardo, Higgins John, Holm Bari, Reitz Bruce, Zhou Yong-Jie, Morris Randall E, O'Shea John J, Borie Dominic C
机构信息
Immunology Group, Department of Antibacterials and Immunology, Pfizer Global Researchand Development, Groton, CT 06340, USA.
出版信息
Science. 2003 Oct 31;302(5646):875-8. doi: 10.1126/science.1087061.
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.
由于其对多种细胞因子信号传导的需求，Janus激酶3（JAK3）是临床免疫抑制的一个理想靶点。我们报告了一种特异性、口服活性的JAK3抑制剂CP-690,550的研发情况，该抑制剂在心脏移植小鼠模型和接受肾移植的食蟹猴中显著延长了生存期。CP-690,550治疗与高血压、高脂血症或淋巴增殖性疾病无关。基于这些临床前结果，我们认为CP-690,550阻断JAK3在人体器官移植及其他临床环境中具有实现治疗性理想免疫抑制的潜力。
Zotero 插件