Prevention of Organ Allograft Rejection by a Specific Janus Kinase 3 Inhibitor
Author:
Changelian Paul S.12345, Flanagan Mark E.12345, Ball Douglas J.12345, Kent Craig R.12345, Magnuson Kelly S.12345, Martin William H.12345, Rizzuti Bonnie J.12345, Sawyer Perry S.12345, Perry Bret D.12345, Brissette William H.12345, McCurdy Sandra P.12345, Kudlacz Elizabeth M.12345, Conklyn Maryrose J.12345, Elliott Eileen A.12345, Koslov Erika R.12345, Fisher Michael B.12345, Strelevitz Timothy J.12345, Yoon Kwansik12345, Whipple David A.12345, Sun Jianmin12345, Munchhof Michael J.12345, Doty John L.12345, Casavant Jeffrey M.12345, Blumenkopf Todd A.12345, Hines Michael12345, Brown Matthew F.12345, Lillie Brett M.12345, Subramanyam Chakrapani12345, Shang-Poa Chang12345, Milici Anthony J.12345, Beckius Gretchen E.12345, Moyer James D.12345, Su Chunyan12345, Woodworth Thasia G.12345, Gaweco Anderson S.12345, Beals Chan R.12345, Littman Bruce H.12345, Fisher Douglas A.12345, Smith James F.12345, Zagouras Panayiotis12345, Magna Holly A.12345, Saltarelli Mary J.12345, Johnson Kimberly S.12345, Nelms Linda F.12345, Des Etages Shelley G.12345, Hayes Lisa S.12345, Kawabata Thomas T.12345, Finco-Kent Deborah12345, Baker Deanna L.12345, Larson Michael12345, Si Ming-Sing12345, Paniagua Ricardo12345, Higgins John12345, Holm Bari12345, Reitz Bruce12345, Zhou Yong-Jie12345, Morris Randall E.12345, O'Shea John J.12345, Borie Dominic C.12345
Affiliation:
1. Immunology Group, Department of Antibacterials and Immunology, Pfizer Global Researchand Development, Groton, CT 06340, USA. 2. Department of Drug Safety Evaluation, Pfizer Global Researchand Development, Groton, CT 06340, USA. 3. Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Researchand Development, Groton, CT 06340, USA. 4. Department of Genomic and Proteomic Sciences, Pfizer Global Researchand Development, Groton, CT 06340, USA. 5. Transplantation Immunology Laboratory, Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Abstract
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 prolongedsurvival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associatedwith 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 andin other clinical settings.
Publisher
American Association for the Advancement of Science (AAAS)
Subject
Multidisciplinary
Cited by
612 articles.
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