Abstract
Interleukin-2 inducible T-cell kinase (ITK) is a member of the Tec kinase family and is involved with T-cell activation and proliferation. Due to its critical role in acting as a modulator of T-cells, ITK inhibitors could provide a novel route to anti-inflammatory therapy. This work describes the discovery of ITK inhibitors through structure-based design where high-resolution crystal structural information was used to optimize interactions within the kinase specificity pocket of the enzyme to improve both potency and selectivity.
MeSH terms
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Amino Acid Motifs
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Anti-Inflammatory Agents / pharmacology
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Benzimidazoles / chemical synthesis
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Benzimidazoles / pharmacology
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Chemistry, Pharmaceutical / methods*
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Crystallography, X-Ray / methods
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Drug Design
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology*
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Humans
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Inhibitory Concentration 50
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Models, Chemical
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Molecular Conformation
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Protein-Tyrosine Kinases / metabolism*
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Pyridines / chemistry
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents
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Benzimidazoles
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Enzyme Inhibitors
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Pyridines
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benzimidazole
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Tec protein-tyrosine kinase
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Protein-Tyrosine Kinases
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emt protein-tyrosine kinase
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pyridine