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

Lookup NU author(s): Professor Mike Waring, Dr James Smith

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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.


Publication metadata

Author(s): Waring MJ, Andrews DM, Faulder PF, Flemington V, McKelvie JC, Maman S, Preston M, Raubo P, Robb GR, Roberts K, Rowlinson R, Smith JM, Swarbrick ME, Treines I, Winter JG, Wood RJ

Publication type: Article

Publication status: Published

Journal: Chemical Communications

Year: 2014

Volume: 50

Issue: 40

Pages: 5388-5390

Print publication date: 25/05/2014

Online publication date: 13/12/2013

Acceptance date: 12/12/2013

ISSN (print): 1359-7345

ISSN (electronic): 1364-548X

Publisher: Royal Society of Chemistry

URL: http://dx.doi.org/10.1039/C3CC48391F

DOI: 10.1039/C3CC48391F

PubMed id: 24366037

Notes: Invited article - part of themed collection: 2014 Emerging Investigators.


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