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

• DOI: 10.1039/c3cc48391f
• Publication Date: 2013-12-13T11:25:09Z
• 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
• Keywords: Cell Signaling

Two series of inhibitors type III phosphatidylinositol-4-kinase were identified by high throughput screening and optimised to derive probe compounds that independently selectively inhibit the α- β-isoforms with no significant activity towards related kinases in pathway. In a cellular environment, inhibition but not β-subtype led reduction phosphatidylinositol-4-phosphate phosphatidylinositol-4,5-bisphosphate concentration, causing inositol-1-phosphate formation proliferation panel cancer cell lines.