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Related Experiment Videos

Tomoxiprole selectively inhibits cyclooxygenase-2

R E West1, S M Williams, H S She

  • 1Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. robert.west@spcorp.com

Prostaglandins
|April 9, 1998
PubMed
Summary

Tomoxiprole is a potent and selective cyclooxygenase-2 inhibitor with low ulcerogenic potential. This nonsteroidal anti-inflammatory drug demonstrates time-dependent inhibition of cyclooxygenase-2, but not cyclooxygenase-1.

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Area of Science:

  • Pharmacology
  • Biochemistry
  • Medicinal Chemistry

Background:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) often cause gastrointestinal side effects.
  • Cyclooxygenase-2 (COX-2) selective inhibitors are sought to reduce these side effects.
  • Tomoxiprole was previously reported to have low ulcerogenic potential.

Purpose of the Study:

  • To investigate the selectivity of tomoxiprole for cyclooxygenase-2 (COX-2) over cyclooxygenase-1 (COX-1).
  • To characterize the inhibitory profile of tomoxiprole against COX enzymes.

Main Methods:

  • Enzyme inhibition assays using recombinant human COX-2 and COX-1 in transfected COS cells.
  • Enzyme inhibition assays using partially purified ovine COX enzymes.
  • Time-dependency studies for tomoxiprole's inhibitory effects.

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Main Results:

  • Tomoxiprole potently inhibited recombinant human COX-2 (IC50 = 7 nM) compared to COX-1 (IC50 = 240 nM).
  • Similar selectivity was observed with ovine COX enzyme preparations.
  • Tomoxiprole exhibited time-dependent inhibition of COX-2, but not COX-1.

Conclusions:

  • Tomoxiprole is a highly potent and selective inhibitor of cyclooxygenase-2.
  • The compound's selectivity and time-dependent inhibition profile align with expectations for a COX-2-sparing NSAID.
  • Further investigation into tomoxiprole as a potential therapeutic agent with reduced gastrointestinal toxicity is warranted.