Discovery of potent, selective small molecule inhibitors of α-subtype of type III phosphatidylinositol-4-kinase (PI4KIIIα). Issue 16 (15th August 2015)

• Record Type: Journal Article
• Authors: Raubo, Piotr; Andrews, David M.; McKelvie, Jennifer C.; Robb, Graeme R.; Smith, James M.; Swarbrick, Martin E.; Waring, Michael J.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 16(2015)
• Page Start: 3189
• Page End: 3193
• Publication Date: 2015-08-15
• Subjects: PI4Kα -- In vitro tools -- IP1 -- Oncology; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.05.093
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.