Therapeutic potential of Janus kinase 3 (JAK3) inhibitors

被引:24
作者
Cetkovic-Cyrlje, M
Tibbles, HE
机构
[1] Parker Hughes Inst, Dept Immunol, St Paul, MN 55113 USA
[2] Parker Hughes Inst, Dept Biochem, St Paul, MN 55113 USA
[3] Parker Hughes Inst, Dept Hematol, St Paul, MN 55113 USA
[4] Parker Hughes Canc Ctr, St Paul, MN 55113 USA
关键词
D O I
10.2174/1381612043384529
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Here we discuss the therapeutic potential of Janus kinase 3 (JAK3) inhibitors as a new class of immunomodulatory agents with immunosuppressive, anti-inflammatory, anti-allergic, anti-thrombotic and anti-leukemic properties. JAKs are abundantly expressed in primary leukemic cells from children with ALL (acute lymphoblastic leukemia) and are crucial for signals regulating apoptosis. Additional roles for JAK3 in mast cell-mediated immediate hypersensitivity reactions, autoimmune disorders and platelet function have recently been described. The preclinical studies on JAK3 inhibitors revealed their clinical potential as anti-leukemic agents with anti-thrombotic, anti-allergic and immunosuppressive properties. Results from multiple preclinical experimental model systems of autoimmune diabetes, pancreatic islet transplantation, solid organ transplantation, allergy, thrombosis and bone marrow transplantation are discussed in the context of the clinical need for new immunomodulatory agents with such properties.
引用
收藏
页码:1767 / 1784
页数:18
相关论文
共 227 条
[1]   5-LIPOXYGENASE-ACTIVATING PROTEIN STIMULATES THE UTILIZATION OF ARACHIDONIC-ACID BY 5-LIPOXYGENASE [J].
ABRAMOVITZ, M ;
WONG, E ;
COX, ME ;
RICHARDSON, CD ;
LI, C ;
VICKERS, PJ .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1993, 215 (01) :105-111
[2]  
AIZAWA S, 1995, BONE MARROW TRANSPL, V16, P603
[3]  
AN S, 1998, ALLERGY PRINCIPLES P
[4]  
APPERLEY JF, 1986, BONE MARROW TRANSPL, V1, P53
[5]   IDENTIFICATION OF JAK2 AS A GROWTH-HORMONE RECEPTOR-ASSOCIATED TYROSINE KINASE [J].
ARGETSINGER, LS ;
CAMPBELL, GS ;
YANG, XN ;
WITTHUHN, BA ;
SILVENNOINEN, O ;
IHLE, JN ;
CARTERSU, C .
CELL, 1993, 74 (02) :237-244
[6]   THE PATHOBIOLOGY OF BRONCHIAL-ASTHMA [J].
ARM, JP ;
LEE, TH .
ADVANCES IN IMMUNOLOGY, 1992, 51 :323-382
[7]   A PROSPECTIVE RANDOMIZED TRIAL OF CYCLOSPORINE AND METHOTREXATE VERSUS CYCLOSPORINE, METHOTREXATE AND PREDNISOLONE FOR PREVENTION OF GRAFT-VERSUS-HOST DISEASE AFTER HLA-IDENTICAL SIBLING MARROW TRANSPLANTATION FOR HEMATOLOGICAL MALIGNANCY [J].
ATKINSON, K ;
BIGGS, J ;
CONCANNON, A ;
DODDS, A ;
YOUNG, S ;
WILSON, F ;
ASHBY, M ;
DOWNS, K .
AUSTRALIAN AND NEW ZEALAND JOURNAL OF MEDICINE, 1991, 21 (06) :850-856
[8]   Tolerance to islet autoantigens in type 1 diabetes [J].
Bach, JF ;
Chatenoud, L .
ANNUAL REVIEW OF IMMUNOLOGY, 2001, 19 :131-161
[9]  
BAEDER WL, 1992, CLIN EXP IMMUNOL, V89, P174
[10]   Concomitant inhibition of janus kinase 3 and calcineurin-dependent signaling pathways synergistically prolongs the survival of rat heart allografts [J].
Behbod, F ;
Erwin-Cohen, RA ;
Wang, ME ;
Trawick, BW ;
Qu, X ;
Verani, R ;
Kahan, BD ;
Stepkowski, SM ;
Kirken, RA .
JOURNAL OF IMMUNOLOGY, 2001, 166 (06) :3724-3732