COX inhibitors for airway inflammation.

Sanjay Malhotra, Sangram Shesharao Deshmukh, Sunanda Ghosh Dastidar

Daiichi Sankyo India Pharma Private Ltd., Department of Chemistry, Haryana, India. sanjay.malhotra.s8@dsin.co.in

Expert opinion on therapeutic targets 2012 Feb

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The cyclooxygenase (COX) enzyme, which is responsible for the production of prostaglandins (PGs), key mediators of inflammation, may have the potential to become an attractive target for anti-inflammatory therapy. COX catalyzes the conversion of arachidonic acid (AA) into PGs, which play a significant role in disease. PGs are lipid mediators of central importance in the regulation of inflammation and smooth muscle tone. Airway-resident inflammatory cells release PGs: PGD2 and PDF2a amplify smooth muscle contraction and airway inflammation. Following its conversion from membrane phospholipids by phospholipase, AA enters the prostanoid pathway via COX, which catalyzes the conversion of AA to PGH2. PGH2 is then converted to biologically active PGs by cell-specific PG synthases. As COX is the rate limiting step in the PG pathway, the regulation of this enzyme is of critical importance in PG production. This review addresses the opportunities and challenges of COX inhibitors as therapeutic targets in airway inflammation. The review covers literature from the past 20 years. Current literature favors COX inhibitors as potential targets for airway diseases. However, from the information available, it is not clear whether the COX enzyme by itself can serve as a target in drug development for asthma and COPD. Therefore, additional research is required to elucidate the mechanisms of action of COX metabolites before it can be considered as a target.

Citation

Sanjay Malhotra, Sangram Shesharao Deshmukh, Sunanda Ghosh Dastidar. COX inhibitors for airway inflammation. Expert opinion on therapeutic targets. 2012 Feb;16(2):195-207