Abstract
The need for improved specificity and lower toxicity in immune-suppressive drugs for organ transplantation has focused attention on the intracellular signaling pathways that regulate the immune responses of lymphocytes. Among these, the Janus kinase 3 (JAK3) has particular potential, because it mediates signals by several key cytokines, which each utilize a common gamma chain. Changelian et al. developed a highly selective, low-molecular-weight inhibitor of JAK3 that significantly extended organ allograft survival in primate and mouse organ transplant models after oral administration. P. S. Changelian, M. E. Flanagan, D. J. Ball, C. R. Kent, K. S. Magnuson, W. H. Martin, B. J. Rizzuti, P. S. Sawyer, B. D. Perry, W. H. Brissette, S. P. McCurdy, E. M. Kudlacz, M. J. Conklyn, E. A. Elliott, E. R. Koslov, M. B. Fisher, T. J. Strelevitz, K. Yoon, D. A. Whipple, J. Sun, M. J. Munchhof, J. L. Doty, J. M. Casavant, T. A. Blumenkopf, M. Hines, M. F. Brown, B. M. Lillie, C. Subramanyam, C. Shang-Poa, A. J. Milici, G. E. Beckius, J. D. Moyer, C. Su, T. G. Woodworth, A. S. Gaweco, C. R. Beals, B. H. Littman, D. A. Fisher, J. F. Smith, P. Zagouras, H. A. Magna, M. J. Saltarelli, K. S. Johnson, L. F. Nelms, S. G. Des Etages, L. S. Hayes, T. T. Kawabata, D. Finco-Kent, D. L. Baker, M. Larson, M.-S. Si, R. Paniagua, J. Higgins, B. Holm, B. Reitz, Y.-J. Zhou, R. E. Morris, J. J. O'Shea, D. C. Borie, Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 302 , 875-878 (2003). [Abstract] [Full Text]
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