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

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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

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

Science. 2003 Oct 31;302(5646):875-8.

PubMed ID

14593182 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Tofacitinib	Tyrosine-protein kinase JAK2	IC 50 (nM)	20	N/A	N/A	Details