Prevention of Organ Allograft Rejection by a Specific Janus Kinase 3 Inhibitor
Paul S. Changelian(Pfizer (United States)), Mark E. Flanagan(Pfizer (United States)), Douglas J. Ball(Pfizer (United States)), Craig R. Kent(Pfizer (United States)), Kelly S. Magnuson(Pfizer (United States)), William H. Martin(Pfizer (United States)), Bonnie J. Rizzuti(Pfizer (United States)), Perry S. Sawyer(Pfizer (United States)), Bret D. Perry(Pfizer (United States)), William H. Brissette(Pfizer (United States)), Sandra P. McCurdy(Pfizer (United States)), Elizabeth M. Kudlacz(Pfizer (United States)), Maryrose J. Conklyn(Pfizer (United States)), Eileen A. Elliott(Pfizer (United States)), Erika R. Koslov(Pfizer (United States)), Michael B. Fisher(Pfizer (United States)), Timothy J. Strelevitz(Pfizer (United States)), Kwansik Yoon(Pfizer (United States)), David A. Whipple(Pfizer (United States)), Jianmin Sun(Pfizer (United States)), Michael J. Munchhof(Pfizer (United States)), John L. Doty(Pfizer (United States)), Jeffrey Casavant(Pfizer (United States)), Todd A. Blumenkopf(Pfizer (United States)), Michael H. Hines(Pfizer (United States)), Matthew F. Brown(Pfizer (United States)), Brett M. Lillie(Pfizer (United States)), Chakrapani Subramanyam(Pfizer (United States)), Chang Shang-Poa(Pfizer (United States)), Anthony J. Milici(Pfizer (United States)), Gretchen E. Beckius(Pfizer (United States)), James D. Moyer(Pfizer (United States)), Chunyan Su(Pfizer (United States)), Thasia Woodworth(Pfizer (United States)), Anderson S. Gaweco(Pfizer (United States)), Chan Beals(Pfizer (United States)), Bruce H. Littman(Pfizer (United States)), Douglas A. Fisher(Pfizer (United States)), James F. Smith(Pfizer (United States)), Panayiotis Zagouras(Pfizer (United States)), Holly A. Magna(Pfizer (United States)), Mary Saltarelli(Pfizer (United States)), Kimberly S. Johnson(Pfizer (United States)), Linda Nelms(Pfizer (United States)), Shelley G. Des Etages(Pfizer (United States)), Lisa S. Hayes(Pfizer (United States)), Thomas T. Kawabata(Pfizer (United States)), Deborah Finco‐Kent(Pfizer (United States)), Deanna L. Baker(Pfizer (United States)), Michael J. Larson(Pfizer (United States)), Ming‐Sing Si(Pfizer (United States)), Ricardo Paniagua(Pfizer (United States)), John Higgins(Pfizer (United States)), Bari Holm(Pfizer (United States)), Bruce A. Reitz(Pfizer (United States)), Yong-Jie Zhou(National Institutes of Health), Randall E. Morris(National Institutes of Health), John J. O’Shea(National Institutes of Health), Dominic Borie(Pfizer (United States))
Cited by 670Open Access
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.
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