4oty | pdb_00004oty
Crystal structure of lumiracoxib bound to the apo-mouse-cyclooxygenase-2
Structural highlights
FunctionPGH2_MOUSE Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.[1] [2] [3] [4] Publication Abstract from PubMedLumiracoxib is a substrate-selective inhibitor of endocannabinoid oxygenation by cyclooxygenase-2 (COX-2). We assayed a series of lumiracoxib derivatives to identify the structural determinants of substrate-selective inhibition. The hydrogen-bonding potential of the substituents at the ortho positions of the aniline ring dictated the potency and substrate selectivity of the inhibitors. The presence of a 5'-methyl group on the phenylacetic acid ring increased the potency of molecules with a single ortho substituent. Des-fluorolumiracoxib (2) was the most potent and selective inhibitor of endocannabinoid oxygenation. The positioning of critical substituents in the binding site was identified from a 2.35A crystal structure of lumiracoxib bound to COX-2. Exploring the molecular determinants of substrate-selective inhibition of cyclooxygenase-2 by lumiracoxib.,Windsor MA, Valk PL, Xu S, Banerjee S, Marnett LJ Bioorg Med Chem Lett. 2013 Nov 1;23(21):5860-5864. doi:, 10.1016/j.bmcl.2013.08.097. Epub 2013 Sep 6. PMID:24060487[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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