COX-2 selectivity and inflammatory processes.
Increasing amounts of experimental and clinical data support the role of selective cyclooxygenase (COX)-2 inhibition in anti-inflammatory processes and the involvement of COX-1 inhibition in the side effects associated with non steroidal anti-inflammatory drug use. This review will focus on the differences in the structure of the COX-1 and COX-2 molecules, particularly the active site and how they are bound by various NSAIDs to achieve COX-2 selectivity. This COX-2 selectivity will then be characterized in pharmacological assays in vitro and in animal models in vivo. Finally, clinical information available for this new class of selective inhibitors will be discussed.
van Ryn
J
J
Department of Pulmonary Research, Boehringer Ingelheim Pharma KG, Biberach/Riss, Germany. joanne.vanryn@bc.boehringer-ingelheim.com
Trummlitz
G
G
Pairet
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002384:Catalysis; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D007249:Inflammation / Q000201:enzymology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse