J Med Chem. 2006 Nov 16;49(23):6768-78.

In silico-guided target identification of a scaffold-focused library: 1,3,5-triazepan-2,6-diones as novel phospholipase A2 inhibitors.

Muller P, Lena G, Boilard E, Bezzine S, Lambeau G, Guichard G, Rognan D.

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Bioinformatics of the Drug, CNRS UMR 7175, F-67400 Illkirch, and Immunologie et Chimie Thérapeutiques, CNRS UPR 9021, Institut de Biologie Moléculaire et Cellulaire (IBMC), F-67084 Strasbourg Cedex, France.

Abstract

A collection of 2150 druggable active sites from the Protein Data Bank was screened by high-throughput docking to identify putative targets for five representative molecules of a combinatorial library sharing a 1,3,5-triazepan-2,6-dione scaffold. Five targets were prioritized for experimental evaluation by computing enrichment in individual protein entries among the top 2% scoring targets. Out of the five proposed proteins, secreted phospholipase A2 (sPLA2) was shown to be a true target for a panel of 1,3,5-triazepan-2,6-diones which exhibited micromolar affinities toward two human sPLA2 members.

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In silico-guided target identification of a scaffold-focused library: 1,3,5-triazepan-2,6-diones as novel phospholipase A2 inhibitors.
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