2. Academic Validation
  3. Discovery of potent, selective small molecule inhibitors of α-subtype of type III phosphatidylinositol-4-kinase (PI4KIIIα)

Discovery of potent, selective small molecule inhibitors of α-subtype of type III phosphatidylinositol-4-kinase (PI4KIIIα)

  • Bioorg Med Chem Lett. 2015 Aug 15;25(16):3189-93. doi: 10.1016/j.bmcl.2015.05.093.
Piotr Raubo 1,  David M Andrews 2,  Jennifer C McKelvie 3,  Graeme R Robb 2,  James M Smith 4,  Martin E Swarbrick 5,  Michael J Waring 2
Affiliations

Affiliations

  • 1 AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK. Electronic address: [email protected].
  • 2 AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK.
  • 3 Cancer Research Technology, London BioScience Innovation Centre, 2 Royal College Street, London NW1 0NH, UK.
  • 4 AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK; Cancer Research Technology, Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • 5 Cancer Research Technology, Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, UK.
PMID: 26087940 DOI: 10.1016/j.bmcl.2015.05.093
Abstract

The discovery and optimisation of novel, potent and selective small molecule inhibitors of the α-isoform of type III phosphatidylinositol-4-kinase (PI4Kα) are described. Lead compounds show cellular activity consistent with their PI4Kα potency inhibiting the accumulation of IP1 after PDGF stimulation and reducing cellular PIP, PIP2 and PIP3 levels. Hence, these compounds are useful in vitro tools to delineate the complex biological pathways involved in signalling through PI4Kα.

Keywords

IP1; In vitro tools; Oncology; PI4Kα.

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