This mutation appears to contribute to COX-2 selectivity by creating steric hindrance between the sulfonamide oxygen and the methyl group of Ile523 that effectively destabilizes the celecoxib-COX-1 complex. History
It was initially marketed by Pfizer for arthritis. 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.Two lawsuits arose over discovery of celecoxib. Daniel L. Simmons of Brigham Young University (BYU) discovered the COX-2 enzyme in 1988, and in 1991, BYU entered into a collaboration with Monsanto to develop drugs to inhibit it. Monsantos pharmaceutical division was later purchased by Pfizer, and in 2006, BYU sued Pfizer for breach of contract, claiming Pfizer did not properly pay contractual royalties back to BYU. A settlement was reached in April 2012, in which Pfizer agreed to pay $450 million. Other important discoveries in COX-2 were made at University of Rochester, which patented the discoveries. When the patent issued, the university sued Searle (later Pfizer) in a case called, University of Rochester v. G.D. Searle & Co., 358 F.3d 916 (Fed. Cir. 2004).
In some cases it can come on suddenly or following a fall, sudden abduction of the thighs (opening too wide too quickly) or an action that has strained the joint. PGP can begin as early as the first trimester of pregnancy. Pain is usually felt low down over the symphyseal joint, and this area may be extremely tender to the touch. Pain may also be felt in the hips, groin and lower abdomen and can radiate down the inner thighs. Women with PGP may begin to waddle or shuffle, and may be aware of an audible clicking sound coming from the pelvis. PGP can develop slowly during pregnancy, gradually gaining in severity as the pregnancy progresses. During pregnancy and postpartum, the symphyseal gap can be felt moving or straining when walking, climbing stairs or turning over in bed; these activities can be difficult or even impossible. The pain may remain static, e.g., in one place such as the front of the pelvis, producing the feeling of having been kicked; in other cases it may start in one area and move to other areas. It is also possible that a woman may experience a combination of symptoms. Any weight bearing activity has the potential of aggravating an already unstable pelvis, producing symptoms that may limit the ability of the woman to carry out many daily activities. She may experience pain involving movements such as dressing, getting in and out of the bath, rolling in bed, climbing the stairs or sexual activity.