Differential inhibition of group IVA and group VIA phospholipases A2 by 2-oxoamides.

Journal of Medicinal Chemistry
Daren StephensG Kokotos

Abstract

Inhibitors of the Group IVA phospholipase A(2) (GIVA cPLA(2)) and GVIA iPLA(2) are useful tools for defining the roles of these enzymes in cellular signaling and inflammation. We have developed inhibitors of GVIA iPLA(2) building upon the 2-oxoamide backbone that are uncharged, containing ester groups. Although the most potent inhibitors of GVIA iPLA(2) also inhibited GIVA cPLA(2), there were three 2-oxoamide compounds that selectively and weakly inhibited GVIA iPLA(2). We further show that several potent 2-oxoamide inhibitors of GIVA cPLA(2) containing free carboxylic groups (Kokotos et al. J. Med. Chem. 2002, 45, 2891-2893) do not inhibit GVIA iPLA(2) and are, therefore, selective GIVA cPLA(2) inhibitors.

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Citations

Dec 5, 2008·Journal of Medicinal Chemistry·Constantinos BaskakisGeorge Kokotos
Apr 8, 2010·Journal of Medicinal Chemistry·George KokotosEdward A Dennis
Aug 27, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rubèn López-ValesSamuel David
Dec 25, 2015·The Journal of Pharmacology and Experimental Therapeutics·Shiho KanaiSatoshi Akiba
Jul 12, 2008·Journal of Peptide Science : an Official Publication of the European Peptide Society·Georgia AntonopoulouGeorge Kokotos
Dec 22, 2009·Expert Opinion on Therapeutic Patents·Victoria Magrioti, George Kokotos
Jan 9, 2013·Expert Opinion on Therapeutic Patents·Victoria Magrioti, George Kokotos
May 30, 2015·Journal of Lipid Research·Sasanka RamanadhamXiaoyong Lei
Jul 17, 2007·Journal of Peptide Science : an Official Publication of the European Peptide Society·Panagiota Moutevelis-MinakakisGeorge Kokotos
Mar 28, 2020·Biomolecules·Giorgos S KoutoulogenisGeorge Kokotos
Aug 25, 2016·The Journal of Biological Chemistry·Edward A Dennis
Jan 21, 2017·Chemical Communications : Chem Comm·Cheng Yang NgYulin Lam
Aug 26, 2014·Journal of Medicinal Chemistry·George KokotosBerit Johansen
Sep 11, 2018·ACS Omega·Anastasia PsarraGeorge Kokotos
Sep 30, 2008·Bioorganic & Medicinal Chemistry Letters·Victoria MagriotiGeorge Kokotos

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