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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2003-4-22
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pubmed:abstractText |
Here we show that Janus kinase (JAK) 3 is an important molecular target for treatment of autoimmune insulin-dependent (type 1) diabetes mellitus. The rationally designed JAK3 inhibitor JANEX-1 exhibited potent immunomodulatory activity and delayed the onset of diabetes in the NOD mouse model of autoimmune type 1 diabetes. Whereas 60% of vehicle-treated control NOD mice became diabetic by 25 weeks, the incidence of diabetes at 25 weeks was only 9% for NOD females treated with daily injections of JANEX-1 (100 mg/kg/day) from Week 10 through Week 25 (P = 0.007). Furthermore, JANEX-1 prevented the development of insulitis and diabetes in NOD-scid/scid females after adoptive transfer of splenocytes from diabetic NOD females. Chemical inhibitors such as JANEX-1 may provide the basis for effective treatment modalities against human type 1 diabetes. To our knowledge, this is the first report of the immunosuppressive activity of a JAK3 inhibitor in the context of an autoimmune disease.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/JAK3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Jak3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Milk Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ovalbumin,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Quinazolines,
http://linkedlifedata.com/resource/pubmed/chemical/STAT5 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/WHI P131
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1521-6616
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
106
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
213-25
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12706408-Adoptive Transfer,
pubmed-meshheading:12706408-Animals,
pubmed-meshheading:12706408-Cytokines,
pubmed-meshheading:12706408-DNA-Binding Proteins,
pubmed-meshheading:12706408-Diabetes Mellitus, Type 1,
pubmed-meshheading:12706408-Dose-Response Relationship, Drug,
pubmed-meshheading:12706408-Enzyme Inhibitors,
pubmed-meshheading:12706408-Female,
pubmed-meshheading:12706408-Interleukin-2,
pubmed-meshheading:12706408-Janus Kinase 3,
pubmed-meshheading:12706408-Lymphocyte Activation,
pubmed-meshheading:12706408-Mice,
pubmed-meshheading:12706408-Mice, Inbred C57BL,
pubmed-meshheading:12706408-Mice, Inbred NOD,
pubmed-meshheading:12706408-Milk Proteins,
pubmed-meshheading:12706408-Ovalbumin,
pubmed-meshheading:12706408-Phosphorylation,
pubmed-meshheading:12706408-Protein-Tyrosine Kinases,
pubmed-meshheading:12706408-Quinazolines,
pubmed-meshheading:12706408-STAT5 Transcription Factor,
pubmed-meshheading:12706408-T-Lymphocytes,
pubmed-meshheading:12706408-Trans-Activators,
pubmed-meshheading:12706408-Tyrosine
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pubmed:year |
2003
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pubmed:articleTitle |
Targeting JAK3 with JANEX-1 for prevention of autoimmune type 1 diabetes in NOD mice.
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pubmed:affiliation |
Department of Immunology, Parker Hughes Institute, 2699 Patton Road, St. Paul, MN 55113, USA.
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pubmed:publicationType |
Journal Article
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