Structural basis for selective inhibition of COX-2 by nimesulide

Nimesulide 1 is a novel nonsteroidal antiinflammatory drug which inhibits t he enzyme cyclooxygenase 2 (COX-2) more selectively than cyclooxygenase 1 ( COX-1). Molecular modelling studies have been carried out on complexes of 1 with COX-1 and with mutants of COX-1 simulating COX-2. These indicate that the mutations I523V and S516A largely contribute to the selectivity. A com parative study with SC-558 2 has also been performed. (C) 1998 Elsevier Sci ence Ltd. All rights reserved.