2. Academic Validation
  3. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor

Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor

  • Science. 2003 Oct 31;302(5646):875-8. doi: 10.1126/science.1087061.
Paul S Changelian 1,  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 Sun,  Michael 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
Affiliations

Affiliation

  • 1 Immunology Group, Department of Antibacterials and Immunology, Pfizer Global Researchand Development, Groton, CT 06340, USA. paul_s_changelian@groton.pfizer.com
PMID: 14593182 DOI: 10.1126/science.1087061
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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