Tomoxiprole selectively inhibits cyclooxygenase-2.
Tomoxiprole is a nonsteroidal anti-inflammatory compound that was reported to have low ulcerogenic potential, a quality that would be expected of a cyclooxygenase-2-selective inhibitor, and, in fact, we find it is selective for this isozyme. In stably transfected COS cells, the compound inhibits recombinant human cyclooxygenase-2 (IC50 = 7 nM) more potently than recombinant cyclooxygenase-1 (IC50 = 240 nM), and similar results are obtained with partially pure ovine enzyme preparations. The compound is thus a very potent as well as selective inhibitor of cyclooxygenase-2. As is true of some other cyclooxygenase-2-selective inhibitors, tomoxiprole inhibition of cyclooxygenase-2 but not cyclooxygenase-1 is time-dependent.
West
R E
RE
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. robert.west@spcorp.com
Williams
S M
SM
She
H S
HS
Carruthers
N I
NI
Egan
R W
RW
Billah
M M
MM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D019556:COS Cells; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D007527:Isoenzymes; D008565:Membrane Proteins; D011994:Recombinant Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C043209:tomoxiprole