Abstract
We describe the identification, SAR, and pharmacology of the src-family selective lck inhibitor A-770041 that prolongs the survival of major histocompatibility mismatched allografts in models of solid organ transplant rejection for greater than 65 days.
MeSH terms
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Animals
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Chemistry, Pharmaceutical / methods
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Crystallography, X-Ray
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Drug Design
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Enzyme Inhibitors / pharmacology
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Graft Rejection / prevention & control*
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Heart Transplantation / methods
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Humans
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Immunophenotyping
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Immunosuppressive Agents / pharmacology*
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Inhibitory Concentration 50
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Kinetics
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
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Major Histocompatibility Complex
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Models, Chemical
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Models, Molecular
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Pharmaceutical Preparations
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Pyrazoles / chemical synthesis*
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Pyrazoles / pharmacology*
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Pyrimidines / chemical synthesis*
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Pyrimidines / pharmacology*
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Rats
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Time Factors
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Transplantation, Homologous / methods
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src-Family Kinases / antagonists & inhibitors*
Substances
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1-methyl-1H-indole-2-carboxylic acid (4-(1-(4-(4-acetylpiperazin-1-yl)cyclohexyl)-4-amino-1H-pyrazolo(3,4-d)pyrimidin-3-yl)-2-methoxyphenyl)amide
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Enzyme Inhibitors
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Immunosuppressive Agents
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Pharmaceutical Preparations
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Pyrazoles
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Pyrimidines
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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src-Family Kinases