Abstract
Two series of inhibitors of type III phosphatidylinositol-4-kinase were identified by high throughput screening and optimised to derive probe compounds that independently and selectively inhibit the α- and the β-isoforms with no significant activity towards related kinases in the pathway. In a cellular environment, inhibition of the α- but not the β-subtype led to a reduction in phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate concentration, causing inhibition of inositol-1-phosphate formation and inhibition of proliferation in a panel of cancer cell lines.
MeSH terms
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1-Phosphatidylinositol 4-Kinase / antagonists & inhibitors*
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Cell Proliferation / drug effects
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High-Throughput Screening Assays
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Humans
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Inositol Phosphates / antagonists & inhibitors*
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Inositol Phosphates / metabolism
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Models, Molecular
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Molecular Structure
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Neoplasms / drug therapy*
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Neoplasms / metabolism
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Neoplasms / pathology
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Phosphatidylinositol 4,5-Diphosphate / metabolism*
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Phosphatidylinositol Phosphates / metabolism*
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Protein Kinase Inhibitors / pharmacology*
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Signal Transduction / drug effects
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Small Molecule Libraries / pharmacology*
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Tumor Cells, Cultured
Substances
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Inositol Phosphates
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Phosphatidylinositol 4,5-Diphosphate
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Phosphatidylinositol Phosphates
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Protein Kinase Inhibitors
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Small Molecule Libraries
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phosphatidylinositol 4-phosphate
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inositol 1-phosphate
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1-Phosphatidylinositol 4-Kinase