Prevention of Organ Allograft Rejection by a Specific Janus Kinase 3 Inhibitor

Paul S. Changelian, Mark E. Flanagan, Douglas J. Ball, Craig R. Kent, Kelly S. Magnuson, William H. Martin, Bonnie J. Rizzuti, Perry S. Sawyer, Bret D. Perry, William H. Brissette, Sandra P. McCurdy, Elizabeth M. Kudlacz, Maryrose J. Conklyn, Eileen A. Elliott, Erika R. Koslov, Michael B. Fisher, Timothy J. Strelevitz, Kwansik Yoon, David A. Whipple, Jianmin SunMichael J. Munchhof, John L. Doty, Jeffrey M. Casavant, Todd A. Blumenkopf, Michael Hines, Matthew F. Brown, Brett M. Lillie, Chakrapani Subramanyam, Chang Shang-Poa, Anthony J. Milici, Gretchen E. Beckius, James D. Moyer, Chunyan Su, Thasia G. Woodworth, Anderson S. Gaweco, Chan R. Beals, Bruce H. Littman, Douglas A. Fisher, James F. Smith, Panayiotis Zagouras, Holly A. Magna, Mary J. Saltarelli, Kimberly S. Johnson, Linda F. Nelms, Shelley G. Des Etages, Lisa S. Hayes, Thomas T. Kawabata, Deborah Finco-Kent, Deanna L. Baker, Michael Larson, Ming Sing Si, Ricardo Paniagua, John Higgins, Bari Holm, Bruce Reitz, Yong Jie Zhou, Randall E. Morris, John J. O'Shea, Dominic C. Borie

Research output: Contribution to journalArticlepeer-review

525 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)875-878
Number of pages4
JournalScience
Volume302
Issue number5646
DOIs
StatePublished - Oct 31 2003

ASJC Scopus subject areas

  • General

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