Discovery of novel class 1 phosphatidylinositide 3-kinases (PI3K) fragment inhibitors through structure-based virtual screening.

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Giordanetto F, Kull B, Dellsen A

Discovery of novel class 1 phosphatidylinositide 3-kinases (PI3K) fragment inhibitors through structure-based virtual screening.

Bioorg Med Chem Lett. 2011 Jan 15;21(2):829-35. doi: 10.1016/j.bmcl.2010.11.087. Epub 2010 Nov 24.

PubMed ID

21169017 [ View in PubMed

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Abstract

The discovery of ligand efficient and lipophilicity efficient fragment inhibitors of class 1 phosphatidylinositide 3-kinases (PI3K) is reported. A fragment version of the AstraZeneca compound bank was docked to a homology model of the PI3K p110beta isoform. Interaction-based scoring of the predicted binding poses served to further prioritise the virtual fragment hits. Experimental screening confirmed potency for a total of 18 fragment inhibitors, belonging to five different structural classes.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Wortmannin	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC 50 (nM)	13	N/A	N/A	Details
Wortmannin	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	IC 50 (nM)	89	N/A	N/A	Details