Abstract
A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure-activity relationships (SARs), selectivity and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 2 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo.
MeSH terms
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Animals
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Antibodies, Monoclonal / drug effects
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Antibodies, Monoclonal / pharmacology
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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Interleukin-2 / biosynthesis
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Jurkat Cells
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Mice
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Molecular Structure
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Receptors, Antigen, T-Cell / drug effects
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Structure-Activity Relationship
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Thiazoles / chemical synthesis
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Thiazoles / chemistry
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Thiazoles / pharmacology*
Substances
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Antibodies, Monoclonal
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Enzyme Inhibitors
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Interleukin-2
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Receptors, Antigen, T-Cell
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Thiazoles
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Protein-Tyrosine Kinases
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emt protein-tyrosine kinase