Issue 40, 2014

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.

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

Supplementary files

Article information

Article type
Communication
Submitted
01 11 2013
Accepted
12 12 2013
First published
13 12 2013

Chem. Commun., 2014,50, 5388-5390

Author version available

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

M. J. Waring, D. M. Andrews, P. F. Faulder, V. Flemington, J. C. McKelvie, S. Maman, M. Preston, P. Raubo, G. R. Robb, K. Roberts, R. Rowlinson, J. M. Smith, M. E. Swarbrick, I. Treinies, J. J. G. Winter and R. J. Wood, Chem. Commun., 2014, 50, 5388 DOI: 10.1039/C3CC48391F

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