title: Phosphoinositide-3-kinase (PI3K) inhibitors: identification of new scaffolds using virtual screening.
abstract: In the present work, we used virtual screening (VS) of the ZINC database of 2.5 million compounds to seek new PI3K inhibitory scaffolds. The VS flowchart implemented various filters, including a 3D-database screen, and extensive docking studies, to derive 89 derivatives that were experimentally assayed against the four PI3K isoforms. Seven compounds showed inhibitory activities between 1 and 100 microM, with four being sufficiently potent to constitute potential new scaffolds. The binding conformations of these four were analyzed to provide a rationalization of their activity profile.
authors.affiliation: Auckland Cancer Society Research Centre (ACSRC), School of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1020, New Zealand. raphael.frederick@gmail.com
authors.forename: Raphaël
authors.initials: R
authors.lastname: Frédérick
authors.forename: Claire
authors.initials: C
authors.lastname: Mawson
authors.forename: Jackie D
authors.initials: JD
authors.lastname: Kendall
authors.forename: Claire
authors.initials: C
authors.lastname: Chaussade
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Rewcastle
authors.forename: Peter R
authors.initials: PR
authors.lastname: Shepherd
authors.forename: William A
authors.initials: WA
authors.lastname: Denny
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D016208:Databases, Factual; D055808:Drug Discovery; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020033:Protein Isoforms; D047428:Protein Kinase Inhibitors