Cyclooxygenase 2 inhibitors: discovery, selectivity and the future.

Marnett LJ, Kalgutkar AS
Trends Pharmacol Sci. 1999 20 (11): 465-9

PMID: 10542447 · DOI:10.1016/s0165-6147(99)01385-1

The recent marketing of two selective cyclooxygenase 2 (COX-2) inhibitors climaxes the first phase of an exciting and fast-paced effort to exploit a novel molecular target for nonsteroidal anti-inflammatory drugs (NSAIDs). Much has been written in the lay and scientific press about the potential of COX-2 inhibitors as anti-inflammatory and analgesic agents that lack the gastrointestinal side-effects of traditional NSAIDs. Although research on COX-2 inhibitors has focussed mainly on inflammation and pain, experimental and epidemiological data suggest that COX-2 inhibitors could be used in the treatment or prevention of a broader range of diseases. In this review, some key points and unresolved issues related to the discovery of COX-2 inhibitors, the kinetic and structural basis for their selectivity, and possible complications in their development and use will be discussed.

MeSH Terms (9)

Animals Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors Humans Isoenzymes Membrane Proteins Prostaglandin-Endoperoxide Synthases Protein Conformation

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