Aspirin and steroids: new mechanistic findings and avenues for drug discovery.
The inflammatory response is a life-saving protective process mounted by the body to overcome pathogen infection and injury; however, in chronic inflammatory pathologies, this response can become deregulated. Aspirin and glucocorticoids are two examples of drugs developed over the years to rectify deregulated inflammatory reactions. Interestingly, both these prototypes of anti-inflammatory therapeutics have been 'borrowed' from Mother Nature, identified from the plant and animal world, respectively. In the past century, systematic organic chemistry has been the major approach for producing new drugs, and vast quantities of aspirin and prednisolone have been synthesized, packaged and sold. However, the fascination provoked by these often life-saving drugs has not subsided, and recent work into the endogenous control of the host inflammatory response has revitalized these compounds. Thus, epi-lipoxins, produced after aspirin acetylation of inducible cyclooxygenase-2, and glucocorticoid-regulated annexin 1 appear to be important endogenous mediators of their respective anti-inflammatory effects. In addition, aspirin-triggered epi-lipoxins and glucocorticoid-regulated annexin 1 might act on the same G-protein-coupled receptor, thus rendering this shared receptor a more likely and worthwhile target for fruitful drug discovery.
Gilroy
Derek W
DW
Centre for Clinical Pharmacology and Therapeutics, BHF Laboratories, Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, UK. d.gilroy@ucl.ac.uk
Perretti
Mauro
M
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000627:therapeutic use; D001241:Aspirin / Q000138:chemical synthesis / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D011239:Prednisolone / Q000138:chemical synthesis / Q000627:therapeutic use*; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000639:trends
D000893:Anti-Inflammatory Agents; D011239:Prednisolone; D001241:Aspirin