<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="6.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">A. Viegas</style></author><author><style face="normal" font="default" size="100%">Manso, J.</style></author><author><style face="normal" font="default" size="100%">Corvo, Mc</style></author><author><style face="normal" font="default" size="100%">M.M. Marques</style></author><author><style face="normal" font="default" size="100%">E. J. Cabrita</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Binding of ibuprofen, ketorolac, and diclofenac to COX-1 and COX-2 studied by saturation transfer difference NMR</style></title><secondary-title><style face="normal" font="default" size="100%">J Med Chem</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals Binding</style></keyword><keyword><style  face="normal" font="default" size="100%">Competitive Catalytic Domain Cyclooxygenase 1/*chemistry Cyclooxygenase 2/*chemistry Cyclooxygenase Inhibitors/*chemistry Diclofenac/*chemistry Female Ibuprofen/*chemistry Ketorolac/*chemistry Magnetic Resonance Spectroscopy Male Sheep</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/22091869</style></url></web-urls></urls><number><style face="normal" font="default" size="100%">24</style></number><volume><style face="normal" font="default" size="100%">54</style></volume><pages><style face="normal" font="default" size="100%">8555-62</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Saturation transfer difference NMR (STD-NMR) spectroscopy has emerged as a powerful screening tool and a straightforward way to study the binding epitopes of active compounds in early stage lead discovery in pharmaceutical research. Here we report the application of STD-NMR to characterize the binding of the anti-inflammatory drugs ibuprofen, diclofenac, and ketorolac to COX-1 and COX-2. Using well-studied COX inhibitors and by comparing STD signals with crystallographic structures, we show that there is a relation between the orientations of ibuprofen and diclofenac in the COX-2 active site and the relative STD responses detected in the NMR experiments. On the basis of this analysis, we propose that ketorolac should bind to the COX-2 active site in an orientation similar to that of diclofenac. We also show that the combination of STD-NMR with competition experiments constitutes a valuable tool to address the recently proposed behavior of COX-2 as functional heterodimers and complements enzyme activity studies in the effort to rationalize COX inhibition mechanisms.&lt;/p&gt;
</style></abstract><work-type><style face="normal" font="default" size="100%">Journal Article</style></work-type><notes><style face="normal" font="default" size="100%">n/a</style></notes></record></records></xml>