1. Prevention of Organ Allograft Rejection by a Specific Janus Kinase 3 Inhibitor
- Author
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Deborah Finco-Kent, Panayiotis Zagouras, James F. Smith, Kwansik Yoon, Douglas A. Fisher, Randall E. Morris, Jeffrey M. Casavant, Eileen A. Elliott, Dominic C. Borie, William H. Martin, Craig R. Kent, Paul S. Changelian, Linda F. Nelms, John J. O'Shea, Bonnie J. Rizzuti, Anthony J. Milici, Sandra P. McCurdy, Bret D. Perry, Todd Andrew Blumenkopf, Michael John Munchhof, John P. Higgins, Ming-Sing Si, Michael J Larson, William H. Brissette, Chakrapani Subramanyam, Thasia G. Woodworth, Timothy J. Strelevitz, John L. Doty, Bari Holm, Mark Edward Flanagan, Mary Josephine Saltarelli, Gretchen E Beckius, Chunyan Su, Ricardo T. Paniagua, Michael Hines, Chan R. Beals, Johnson Kimberly Sue, Maryrose J. Conklyn, Bruce H. Littman, Kelly S. Magnuson, Holly A. Magna, Perry S. Sawyer, Bruce A. Reitz, Brett M. Lillie, Lisa S. Hayes, Kudlacz Elizabeth M, David A. Whipple, James D. Moyer, Erika R. Koslov, Jianmin Sun, Matthew Frank Brown, Anderson See Gaweco, Yong Jie Zhou, Chang Shang-Poa, Deanna L. Baker, Thomas T. Kawabata, Shelley G. des Etages, Michael B. Fisher, and Douglas J. Ball
- Subjects
Graft Rejection ,medicine.medical_specialty ,Transplantation, Heterotopic ,Filgotinib ,medicine.medical_treatment ,Pharmacology ,Lymphocyte Activation ,Organ transplantation ,Mice ,Piperidines ,Tumor Cells, Cultured ,Animals ,Humans ,Transplantation, Homologous ,Medicine ,Pyrroles ,Lymphocyte Count ,Enzyme Inhibitors ,Kidney transplantation ,Heart transplantation ,Multidisciplinary ,business.industry ,Myocardium ,Janus kinase 3 ,Graft Survival ,Janus Kinase 3 ,Immunosuppression ,Protein-Tyrosine Kinases ,medicine.disease ,Kidney Transplantation ,Lymphocyte Subsets ,Mice, Inbred C57BL ,Transplantation ,Macaca fascicularis ,Pyrimidines ,Gene Expression Regulation ,Mice, Inbred DBA ,Immunology ,Heart Transplantation ,Interleukin-2 ,Lymphocyte Culture Test, Mixed ,business ,Janus kinase ,Immunosuppressive Agents - 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.
- Published
- 2003
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