Abstract
Protein kinase C iota (PKC-ι) is an atypical kinase implicated in the promotion of different cancer types. A biochemical screen of a fragment library has identified several hits from which an azaindole-based scaffold was chosen for optimization. Driven by a structure-activity relationship and supported by molecular modeling, a weakly bound fragment was systematically grown into a potent and selective inhibitor against PKC-ι.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carcinoma, Hepatocellular / drug therapy*
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Carcinoma, Hepatocellular / pathology
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Cell Proliferation / drug effects*
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Humans
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Isoenzymes / antagonists & inhibitors*
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Liver Neoplasms / drug therapy*
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Liver Neoplasms / pathology
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Models, Molecular
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Molecular Structure
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Protein Conformation
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Protein Kinase C / antagonists & inhibitors*
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology*
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Tumor Cells, Cultured
Substances
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Isoenzymes
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Protein Kinase Inhibitors
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Protein Kinase C
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protein kinase C lambda