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.
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Authors | Michael J Waring, David M Andrews, Paul F Faulder, Vikki Flemington, Jennifer C McKelvie, Sarita Maman, Marian Preston, Piotr Raubo, Graeme R Robb, Karen Roberts, Rachel Rowlinson, James M Smith, Martin E Swarbrick, Iris Treinies, Jon J G Winter, Robert J Wood |
Journal | Chemical communications (Cambridge, England)
(Chem Commun (Camb))
Vol. 50
Issue 40
Pg. 5388-90
(May 25 2014)
ISSN: 1364-548X [Electronic] England |
PMID | 24366037
(Publication Type: Journal Article)
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Chemical References |
- Inositol Phosphates
- Phosphatidylinositol 4,5-Diphosphate
- Phosphatidylinositol Phosphates
- Protein Kinase Inhibitors
- Small Molecule Libraries
- phosphatidylinositol 4-phosphate
- inositol 1-phosphate
- 1-Phosphatidylinositol 4-Kinase
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Topics |
- 1-Phosphatidylinositol 4-Kinase
(antagonists & inhibitors)
- Cell Proliferation
(drug effects)
- High-Throughput Screening Assays
- Humans
- Inositol Phosphates
(antagonists & inhibitors, metabolism)
- Models, Molecular
- Molecular Structure
- Neoplasms
(drug therapy, metabolism, pathology)
- Phosphatidylinositol 4,5-Diphosphate
(metabolism)
- Phosphatidylinositol Phosphates
(metabolism)
- Protein Kinase Inhibitors
(pharmacology)
- Signal Transduction
(drug effects)
- Small Molecule Libraries
(pharmacology)
- Tumor Cells, Cultured
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