Abstract
The involvement of prostaglandin D2 (PGD2) in inflammatory diseases like allergy and asthma is well established, thus blocking the effect of this mediator represents a novel therapeutic approach for the treatment of such diseases. PGD2 is now known to act through two seven-transmembrane (7TM) receptors, DP (DP1) and CRTH2 (DP2), which are also activated by several endogenous metabolites from the arachidonic acid cascade, making the regulatory system highly complex. There has recently been a considerable effort aimed at developing antagonists of the PGD2 receptors for treatment of inflammatory conditions like asthma and rhinitis. Several potent DP antagonists are now known, and one of these is currently in clinical trials for treatment of asthma. CRTH2 has received much attention since its identification as the second high affinity PGD 2 receptor in 2001, and a number of potent and selective antagonists have recently become available. This review will briefly discuss the biological background and validation of DP and CRTH2 as targets for antiinflammatory drugs, and then highlight developments in medicinal chemistry which have appeared in journals and patent applications in the last few years, and which have brought us closer to therapeutic applications of PGD2 receptor antagonists in various indications.
Keywords: NSAIDs, inflammatory diseases, D Prostanoid Recepto, CRTH2 Agonists, Ramatroban, indomethacin
Current Topics in Medicinal Chemistry
Title: Targeting the Prostaglandin D2 Receptors DP and CRTH2 for Treatment of Inflammation
Volume: 6 Issue: 13
Author(s): Trond Ulven and Evi Kostenis
Affiliation:
Keywords: NSAIDs, inflammatory diseases, D Prostanoid Recepto, CRTH2 Agonists, Ramatroban, indomethacin
Abstract: The involvement of prostaglandin D2 (PGD2) in inflammatory diseases like allergy and asthma is well established, thus blocking the effect of this mediator represents a novel therapeutic approach for the treatment of such diseases. PGD2 is now known to act through two seven-transmembrane (7TM) receptors, DP (DP1) and CRTH2 (DP2), which are also activated by several endogenous metabolites from the arachidonic acid cascade, making the regulatory system highly complex. There has recently been a considerable effort aimed at developing antagonists of the PGD2 receptors for treatment of inflammatory conditions like asthma and rhinitis. Several potent DP antagonists are now known, and one of these is currently in clinical trials for treatment of asthma. CRTH2 has received much attention since its identification as the second high affinity PGD 2 receptor in 2001, and a number of potent and selective antagonists have recently become available. This review will briefly discuss the biological background and validation of DP and CRTH2 as targets for antiinflammatory drugs, and then highlight developments in medicinal chemistry which have appeared in journals and patent applications in the last few years, and which have brought us closer to therapeutic applications of PGD2 receptor antagonists in various indications.
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Cite this article as:
Ulven Trond and Kostenis Evi, Targeting the Prostaglandin D2 Receptors DP and CRTH2 for Treatment of Inflammation, Current Topics in Medicinal Chemistry 2006; 6 (13) . https://dx.doi.org/10.2174/15680266106061427
DOI https://dx.doi.org/10.2174/15680266106061427 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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