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ID: ALA1156056

Journal: Bioorg Med Chem Lett

Title: Phosphoinositide-3-kinase (PI3K) inhibitors: identification of new scaffolds using virtual screening.

Authors: Frédérick R, Mawson C, Kendall JD, Chaussade C, Rewcastle GW, Shepherd PR, Denny WA.

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.

CiteXplore: 19748269

DOI: 10.1016/j.bmcl.2009.08.087