The First Potent Inhibitor of Mammalian Group X Secreted Phospholipase A2: Elucidation of Sites for Enhanced Binding
- 15 April 2006
- journal article
- letter
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 49 (10), 2858-2860
- https://doi.org/10.1021/jm060136t
Abstract
Using the X-ray structure of human group X secreted phospholipase A2 (hGX), we carried out structure-based design of indole-based inhibitors and prepared the compounds using a new synthetic route. The most potent compound inhibited hGX and the mouse orthologue with an IC50 of 75 nM. This compound is the most potent hGX inhibitor reported to date and was also found to inhibit a subset of the other mouse and human sPLA2s.Keywords
This publication has 23 references indexed in Scilit:
- Search of Factors That Intermediate Cytokine-induced Group IIAPhospholipase A2 Expression through the Cytosolic PhospholipaseA2- and 12/15-Lipoxygenase-dependentPathwayOnline Journal of Public Health Informatics, 2005
- Arachidonic Acid Release from Mammalian Cells Transfected with Human Groups IIA and X Secreted Phospholipase A2 Occurs Predominantly during the Secretory Process and with the Involvement of Cytosolic Phospholipase A2-αOnline Journal of Public Health Informatics, 2004
- Role of Group V Phospholipase A2 in Zymosan-induced Eicosanoid Generation and Vascular Permeability Revealed by Targeted Gene DisruptionOnline Journal of Public Health Informatics, 2004
- Group V Phospholipase A2-mediated Oleic Acid Mobilization in Lipopolysaccharide-stimulated P388D1MacrophagesOnline Journal of Public Health Informatics, 2000
- Exogenously Added Human Group X Secreted Phospholipase A2 but Not the Group IB, IIA, and V Enzymes Efficiently Release Arachidonic Acid from Adherent Mammalian CellsJournal of Biological Chemistry, 2000
- Indole Inhibitors of Human Nonpancreatic Secretory Phospholipase A2. 2. Indole-3-acetamides with Additional FunctionalityJournal of Medicinal Chemistry, 1996
- Structure-based design of the first potent and selective inhibitor of human non-pancreatic secretory phospholipase A2Nature Structural & Molecular Biology, 1995
- Discovery of new non-phospholipid inhibitors of the secretory phospholipases A2Journal of Medicinal Chemistry, 1994
- High-level expression in Escherichia coli and rapid purification of enzymatically active honey bee venom phospholipase A2Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1992
- Increased Concentrations of Synovial-Type Phospholipase A2 in Serum and Pulmonary and Renal Complications in Acute PancreatitisDigestion, 1992