Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents

@article{Kurumbail1996StructuralBF,
  title={Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents},
  author={Ravi G. Kurumbail and Anna M. Stevens and James K. Gierse and Joseph J. McDonald and Roderick A. Stegeman and Jina Y. Pak and Daniel Gildehaus and Julie M. iyashiro and Thomas D Penning and Karen Seibert and Peter C. Isakson and William C. Stallings},
  journal={Nature},
  year={1996},
  volume={384},
  pages={644-648}
}
PROSTAGLANDINSand glucocorticoids are potent mediators of inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) exert their effects by inhibition of prostaglandin production. The pharmacological target of NSAIDs is cyclooxygenase (COX, also known as PGH synthase), which catalyses the first committed step in arachidonic-acid metabolism1,2. Two isoforms of the membrane protein COX are known3: COX-1, which is constitu-tively expressed in most tissues, is responsible for the physiological… 

The structure of human cyclooxygenase-2 and selective inhibitors

A hypothesis derived from these discoveries proposes that the undesirable side effects of classical COX inhibitors results from the inhibition of COX-1, whereas the therapeutic, anti-inflammatory effects result from the inhibitedCOX-27.

Recently reported inhibitors of cyclooxygenase-2

Selective COX-2 inhibitors have been demonstrated to be anti-inflammatory and analgesic without causing the gastrointestinal damage associated with current non-selective cyclooxygenase inhibitors.

Inhibitors of cyclooxygenases: mechanisms, selectivity and uses.

  • B. Rm
  • Medicine, Biology
  • 2006
The discovery of cyclooxygenase-2 and the establishment of its structure led to the development of selective inhibitors of this enzyme, such as celecoxib and rofecoxib, with potent anti-inflammatory actions but with reduced gastrotoxic effects.

Structural diversity of selective COX-2 inhibitors

These bioactive lipids mediate numerous physiological and pathophysiological effects, including pain, fever, inflammation, hemostasis, and regulation of renal function and maintenance of mucosal integrity in the stomach.

Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition

Characterization of the two COX isozymes is allowing the discrimination of the roles each play in physiological processes such as homeostatic maintenance of the gastrointestinal tract, renal function, blood clotting, embryonic implantation, parturition, pain, and fever.

Cyclooxygenase-2--10 years later.

  • B. HinzK. Brune
  • Medicine, Biology
    The Journal of pharmacology and experimental therapeutics
  • 2002
The present review assesses recent advances in COX-2 research, with particular emphasis on new insights into pathophysiological and physiological functions of this isoenzyme.

Cyclooxygenase-2 inhibitors in tumorigenesis (Part II).

  • M. Taketo
  • Medicine, Biology
    Journal of the National Cancer Institute
  • 1998
Accumulating evidence indicates that NSAIDs can reduce the incidence of colorectal cancers in human and experimental animals and can reduced the number and size of polyps in patients with familial adenomatous polyposis.

Cyclooxygenases: structural, cellular, and molecular biology.

This review examines how the structures of these enzymes relate mechanistically to cyclooxygenase and peroxidase catalysis, and how differences in the structure of PGHS-2 confer on this isozyme differential sensitivity to COX-2 inhibitors.

Cyclooxygenase inhibitors--current status and future prospects.

...

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