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

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

Research output: Contribution to journalArticle

492 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)875-878
Number of pages4
JournalScience
Volume302
Issue number5646
DOIs
StatePublished - Oct 31 2003

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Janus Kinase 3
Allografts
Immunosuppression
Macaca fascicularis
Organ Transplantation
Heart Transplantation
Hyperlipidemias
Cytokines
Hypertension
Transplants
Kidney
Survival
tofacitinib
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Changelian, P. S., Flanagan, M. E., Ball, D. J., Kent, C. R., Magnuson, K. S., Martin, W. H., ... Borie, D. C. (2003). Prevention of Organ Allograft Rejection by a Specific Janus Kinase 3 Inhibitor. Science, 302(5646), 875-878. https://doi.org/10.1126/science.1087061

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.

In: Science, Vol. 302, No. 5646, 31.10.2003, p. 875-878.

Research output: Contribution to journalArticle

Changelian, PS, Flanagan, ME, Ball, DJ, Kent, CR, Magnuson, KS, Martin, WH, Rizzuti, BJ, Sawyer, PS, Perry, BD, Brissette, WH, McCurdy, SP, Kudlacz, EM, Conklyn, MJ, Elliott, EA, Koslov, ER, Fisher, MB, Strelevitz, TJ, Yoon, K, Whipple, DA, Sun, J, Munchhof, MJ, Doty, JL, Casavant, JM, Blumenkopf, TA, Hines, M, Brown, MF, Lillie, BM, Subramanyam, C, Shang-Poa, C, Milici, AJ, Beckius, GE, Moyer, JD, Su, C, Woodworth, TG, Gaweco, AS, Beals, CR, Littman, BH, Fisher, DA, Smith, JF, Zagouras, P, Magna, HA, Saltarelli, MJ, Johnson, KS, Nelms, LF, Des Etages, SG, Hayes, LS, Kawabata, TT, Finco-Kent, D, Baker, DL, Larson, M, Si, MS, Paniagua, R, Higgins, J, Holm, B, Reitz, B, Zhou, YJ, Morris, RE, O'Shea, JJ & Borie, DC 2003, 'Prevention of Organ Allograft Rejection by a Specific Janus Kinase 3 Inhibitor', Science, vol. 302, no. 5646, pp. 875-878. https://doi.org/10.1126/science.1087061
Changelian PS, Flanagan ME, Ball DJ, Kent CR, Magnuson KS, Martin WH et al. Prevention of Organ Allograft Rejection by a Specific Janus Kinase 3 Inhibitor. Science. 2003 Oct 31;302(5646):875-878. https://doi.org/10.1126/science.1087061
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. / Prevention of Organ Allograft Rejection by a Specific Janus Kinase 3 Inhibitor. In: Science. 2003 ; Vol. 302, No. 5646. pp. 875-878.
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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 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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T1 - Prevention of Organ Allograft Rejection by a Specific Janus Kinase 3 Inhibitor

AU - Changelian, Paul S.

AU - Flanagan, Mark E.

AU - Ball, Douglas J.

AU - Kent, Craig R.

AU - Magnuson, Kelly S.

AU - Martin, William H.

AU - Rizzuti, Bonnie J.

AU - Sawyer, Perry S.

AU - Perry, Bret D.

AU - Brissette, William H.

AU - McCurdy, Sandra P.

AU - Kudlacz, Elizabeth M.

AU - Conklyn, Maryrose J.

AU - Elliott, Eileen A.

AU - Koslov, Erika R.

AU - Fisher, Michael B.

AU - Strelevitz, Timothy J.

AU - Yoon, Kwansik

AU - Whipple, David A.

AU - Sun, Jianmin

AU - Munchhof, Michael J.

AU - Doty, John L.

AU - Casavant, Jeffrey M.

AU - Blumenkopf, Todd A.

AU - Hines, Michael

AU - Brown, Matthew F.

AU - Lillie, Brett M.

AU - Subramanyam, Chakrapani

AU - Shang-Poa, Chang

AU - Milici, Anthony J.

AU - Beckius, Gretchen E.

AU - Moyer, James D.

AU - Su, Chunyan

AU - Woodworth, Thasia G.

AU - Gaweco, Anderson S.

AU - Beals, Chan R.

AU - Littman, Bruce H.

AU - Fisher, Douglas A.

AU - Smith, James F.

AU - Zagouras, Panayiotis

AU - Magna, Holly A.

AU - Saltarelli, Mary J.

AU - Johnson, Kimberly S.

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AU - Des Etages, Shelley G.

AU - Hayes, Lisa S.

AU - Kawabata, Thomas T.

AU - Finco-Kent, Deborah

AU - Baker, Deanna L.

AU - Larson, Michael

AU - Si, Ming Sing

AU - Paniagua, Ricardo

AU - Higgins, John

AU - Holm, Bari

AU - Reitz, Bruce

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