Potent, selective small molecule inhibitors of type III phosphatidylinositol-4-kinase α- but not β-inhibit the phosphatidylinositol signaling cascade and cancer cell proliferation.

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.

DOI: 10.1039/c3cc48391f

Cite this paper

@article{Waring2014PotentSS, title={Potent, selective small molecule inhibitors of type III phosphatidylinositol-4-kinase α- but not β-inhibit the phosphatidylinositol signaling cascade and cancer cell proliferation.}, author={Michael J. Waring and David M. Andrews and Paul F Faulder and Vikki Flemington and Jennifer C. McKelvie and Sarita Maman and Marian Preston and Piotr Raubo and Graeme R Robb and Karen L Roberts and Rachel A. Rowlinson and James Smith and Martin E Swarbrick and Iris Treinies and Jon Winter and Robert J. Wood}, journal={Chemical communications}, year={2014}, volume={50 40}, pages={5388-90} }