@article {RN41,
	title = {Binding of ibuprofen, ketorolac, and diclofenac to COX-1 and COX-2 studied by saturation transfer difference NMR},
	journal = {J Med Chem},
	volume = {54},
	number = {24},
	year = {2011},
	note = {n/a},
	pages = {8555-62},
	type = {Journal Article},
	abstract = {<p>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.</p>
},
	keywords = {Animals Binding, Competitive Catalytic Domain Cyclooxygenase 1/*chemistry Cyclooxygenase 2/*chemistry Cyclooxygenase Inhibitors/*chemistry Diclofenac/*chemistry Female Ibuprofen/*chemistry Ketorolac/*chemistry Magnetic Resonance Spectroscopy Male Sheep},
	issn = {1520-4804 (Electronic) 0022-2623 (Linking)},
	doi = {10.1021/jm201090k},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22091869},
	author = {A. Viegas and Manso, J. and Corvo, Mc and M.M. Marques and E. J. Cabrita}
}
