Abstract
A series of novel cyanopyridyl based molecules (1-14) were designed, synthesized and probed for inhibition of mammalian target of rapamycin (mTOR) activity. Compound 14 was found to be a potent inhibitor of mTOR activity as assessed by enzyme-linked immunoassays and Western blot analysis. Most importantly, systemic application (intraperitoneal; ip) of compound 14 significantly suppressed macroscopic and histological abnormalities associated with chemically-induced murine colitis.
MeSH terms
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Acrylamides / chemical synthesis
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Acrylamides / pharmacokinetics
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Acrylamides / therapeutic use
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Animals
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Cell Line, Tumor
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Colitis, Ulcerative / chemically induced
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Colitis, Ulcerative / drug therapy
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Disease Models, Animal
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Humans
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Mice
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Nitriles / chemical synthesis*
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Nitriles / chemistry
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Nitriles / pharmacokinetics
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / pharmacokinetics
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Protein Kinase Inhibitors / therapeutic use
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Protein Kinases / chemistry
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Protein Kinases / metabolism*
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Pyridines / chemical synthesis*
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Pyridines / pharmacokinetics
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Pyridines / therapeutic use
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TOR Serine-Threonine Kinases
Substances
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Acrylamides
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Nitriles
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Protein Kinase Inhibitors
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Pyridines
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Protein Kinases
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MTOR protein, human
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mTOR protein, mouse
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TOR Serine-Threonine Kinases