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Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor SCIENCE Changelian, P. S., Flanagan, M. E., Ball, D. J., Kent, C. R., Magnuson, K. S., Martin, W. H., Rizzuti, B. J., Sawyer, P. S., Perry, B. D., Brissette, W. H., McCurdy, S. P., Kudlacz, E. M., Conklyn, M. J., Elliott, E. A., Koslov, E. R., Fisher, M. B., Strelevitz, T. J., Yoon, K., Whipple, D. A., Sun, J. M., Munchhof, M. J., Doty, J. L., Casavant, J. M., Blumenkopf, T. A., Hines, M., Brown, M. F., Lillie, B. M., Subramanyam, C., Shang-Poa, C., MILICI, A. J., Beckius, G. E., Moyer, J. D., Su, C. Y., Woodworth, T. G., Gaweco, A. S., Beals, C. R., Littman, B. H., Fisher, D. A., Smith, J. F., Zagouras, P., Magna, H. A., Saltarelli, M. J., Johnson, K. S., Nelms, L. F., Des Etages, S. G., Hayes, L. S., Kawabata, T. T., Finco-Kent, D., Baker, D. L., Larson, M., Si, M. S., Paniagua, R., Higgins, J., Holm, B., Reitz, B., Zhou, Y. J., Morris, R. E., O'Shea, J. J., Borie, D. C. 2003; 302 (5646): 875-878

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.

View details for Web of Science ID 000186258000052

View details for PubMedID 14593182