Designing selective COX-2 inhibitors: molecular modeling approaches.

Molecular modeling approaches have been successfully used to gain insight into the molecular mechanism of selective cyclooxygenase-2 (COX-2) inhibition. These approaches are based on X-ray structure data and results from structure-activity relationships and site-directed mutagenesis experiments. The recognition process of substrates and inhibitors by COX isoenzymes can be visualized by applying algorithms to describe local properties on the enzyme surface, thus allowing key differences in structure to be studied that may confer differential sensitivity to inhibitors. The virtual screening techniques for COX isoenzymes are rapidly improving, and the search for new selective COX-2 inhibitors has been stimulated by the tremendous success of meloxicam, celecoxib and rofecoxib in the pharmaceutical market and their potential use in new indications.