text: The impetus for development of selective COX-2 inhibitors was the adverse gastrointestinal side-effects of NSAIDs. Soon after the discovery of the mechanism of action of NSAIDs, strong indications emerged for alternative forms of COX, but little supporting evidence was found. COX enzyme proved to be difficult to purify and was not sequenced until 1988. In 1991 the existence of the COX-2 enzyme was confirmed by being cloned by Dr. Dan Simmons at Brigham Young University. Before the confirmation of COX-2 existence, the Dupont company had developed a compound, DuP-697, that was potent in many anti-inflammatory assays but did not have the ulcerogenic effects of NSAIDs. Once the COX-2 enzyme was identified, Dup-697 became the building-block for synthesis of COX-2 inhibitors. Celecoxib and rofecoxib, the first COX-2 inhibitors to reach market, were based on DuP-697. It took less than eight years to develop and market the first COX-2 inhibitor, with Celebrex (celecoxib) launched in December 1998 and Vioxx (rofecoxib) launched in May 1999.  Celecoxib and other COX-2 selective inhibitors, valdecoxib, parecoxib, and mavacoxib, were discovered by a team at the Searle division of Monsanto led by John Talley.