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

✍ Scribed by Fabrizio Giordanetto; Bengt Kull; Anita Dellsén


Publisher
Elsevier Science
Year
2011
Tongue
English
Weight
1002 KB
Volume
21
Category
Article
ISSN
0960-894X

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✦ Synopsis


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 p110β 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.