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

Changelian, Paul S.; Flanagan, Mark E.; Ball, Douglas J.; Kent, Craig R.; Magnuson, Kelly S.; Martin, William H.; Rizzuti, Bonnie J.; Sawyer, Perry S.; Perry, Bret D.; Brissette, William H.; McCurdy, Sandra P.; Kudlacz, Elizabeth M.; Conklyn, Maryrose J.; Elliott, Eileen A.; Koslov, Erika R.; Fisher, Michael B.; Strelevitz, Timothy J.; Yoon, Kwansik; Whipple, David A.; Sun, Jianmin; Munchhof, Michael J.; Doty, John L.; Casavant, Jeffrey M.; Blumenkopf, Todd A.; Hines, Michael; Brown, Matthew F.; Lillie, Brett M.; Subramanyam, Chakrapani; Shang-Poa, Chang; Milici, Anthony J.; Beckius, Gretchen E.; Moyer, James D.; Su, Chunyan; Woodworth, Thasia G.; Gaweco, Anderson S.; Beals, Chan R.; Littman, Bruce H.; Fisher, Douglas A.; Smith, James F.; Zagouras, Panayiotis; Magna, Holly A.; Saltarelli, Mary J.; Johnson, Kimberly S.; Nelms, Linda F.; Des Etages, Shelley G.; Hayes, Lisa S.; Kawabata, Thomas T.; Finco-Kent, Deborah; Baker, Deanna L.; Larson, Michael

doi:10.1126/science.1087061

Cited by 607

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

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

Changelian, Paul S., Flanagan, Mark E., Ball, Douglas J., Kent, Craig R., Magnuson, Kelly S., Martin, William H., Rizzuti, Bonnie J., Sawyer, Perry S., Perry, Bret D., Brissette, William H., McCurdy, Sandra P., Kudlacz, Elizabeth M., Conklyn, Maryrose J., Elliott, Eileen A., Koslov, Erika R., Fisher, Michael B., Strelevitz, Timothy J., Yoon, Kwansik, Whipple, David A., Sun, Jianmin, Munchhof, Michael J., Doty, John L., Casavant, Jeffrey M., Blumenkopf, Todd A., Hines, Michael, Brown, Matthew F., Lillie, Brett M., Subramanyam, Chakrapani, Shang-Poa, Chang, Milici, Anthony J., Beckius, Gretchen E., Moyer, James D., Su, Chunyan, Woodworth, Thasia G., Gaweco, Anderson S., Beals, Chan R., Littman, Bruce H., Fisher, Douglas A., Smith, James F., Zagouras, Panayiotis, Magna, Holly A., Saltarelli, Mary J., Johnson, Kimberly S., Nelms, Linda F., Des Etages, Shelley G., Hayes, Lisa S., Kawabata, Thomas T., Finco-Kent, Deborah, Baker, Deanna L., Larson, Michael, Si, Ming-Sing, Paniagua, Ricardo, Higgins, John, Holm, Bari, Reitz, Bruce, Zhou, Yong-Jie, Morris, Randall E., O'Shea, John J., Borie, Dominic C.·2003·Science

DOI 10.1126/science.1087061

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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.

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Sorted by citations

JAKs and STATs in immunity, immunodeficiency, and cancer
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Authors: 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., 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., 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.
Affiliations: Immunology Group, Department of Antibacterials and Immunology, Pfizer Global Researchand Development, Groton, CT 06340, USA.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2003-10-31
Volume: 302
Issue: 5646
Pages: 875-878
ISSN: 0036-8075
1095-9203
DOI: 10.1126/science.1087061
Cited by: 607
References: 1
Language: en

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This page: CoChat. (2026). Citation check: Prevention of Organ Allograft Rejection by a Specific Janus Kinase 3 Inhibitor. https://app.cochat.ai/papers/10.1126/science.1087061
The paper: 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., . . . Borie, D. C. (2003). Prevention of Organ Allograft Rejection by a Specific Janus Kinase 3 Inhibitor. Science. https://doi.org/10.1126/science.1087061

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

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