@article {Kalgutkar:March 2001:1389-4501:79, author = "Kalgutkar A.S.", author = "Zhao Z.", title = "Discovery and Design of Selective Cyclooxygenase-2 Inhibitors as Non-Ulcerogenic, Anti-Inflammatory Drugs with Potential Utility as Anti-Cancer Agents", journal = "Current Drug Targets", volume = "2", year = "March 2001", abstract = "

The recent marketing of two selective cyclooxygenase-2 (COX-2) inhibitors, celecoxib and rofecoxib is remarkable considering that COX-2 was only discovered eight years ago as a growth factor- and cytokine-inducible gene. Concomitant with these pharmaceutical successes is the advances in our understanding of the molecular and structural basis for selective COX-2 inhibition. This review provides a perspective on the ongoing structure-activity relationship (SAR) efforts in the search of COX-2-specific inhibitors with particular reference to their structural basis for isozyme-specific inhibition. In addition to the existing inhibitor classes, this review will also highlight many novel structural classes which have recently emerged due to a better understanding of the active site differences between the two isozymes with a special emphasis on the modification of the well-established non-steroidal anti-inflammatory drug (NSAID) scaffold. In addition to its role in inflammation, recent studies suggest that COX-2-derived prostaglandins may play a pivotal part in the maintenance of tumor viability, growth, and metastasis. In this review, we summarize the NSAID epidemiological evidence, studies demonstrating overexpression of COX-2 in multiple human tumors and pharmacological evidence in animal models, which indicate that COX-2 inhibitors could be used in the prevention or treatment of a broader range of disease.

", pages = "79-106(28)", url = "http://www.ingentaconnect.com/content/ben/cdt/2001/00000002/00000001/art00006" doi = "doi:10.2174/1389450013348830" }