Abstract
Arachidonic acid (ARA) undergoes enzyme-mediated oxidative metabolism, resulting in the formation of anumber of biologically active metabolites. For over a century, these biochemical transformations have been the target ofnumerous pharmacological drugs for inflammation and pain. In particular, non-steroidal anti-inflammatory drugs(NSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors (coxibs) are widely used in the treatment of inflammationand pain. However, gastrointestinal (GI) and cardiovascular adverse effects of NSAIDs and coxibs, and recent findingsdemonstrating that there are significant risks from the disruption of oxylipin levels when pharmacologically inhibiting asingle ARA cascade metabolic pathway, have led to studies involving the simultaneous inhibition of multiple pathways inARA cascade. These studies suggest that multitarget inhibition represents a new and valuable option to enhance efficacyor reduce side-effects in the treatment of inflammation and pain. This review focuses on the crosstalk within the threepathways of the ARA cascade (cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450)), andsummarizes the current and future approaches of multitarget inhibitors for the treatment of eicosanoid driven inflammationand pain.
Keywords:Cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 (CYP), soluble epoxide hydrolase (sEH), multitargetinhibitors, dual inhibitors
Current Medicinal Chemistry
Title:Rationally Designed Multitarget Agents Against Inflammation and Pain
Volume: 20Issue: 13
Author(s):S. H. Hwang, A. T. Wecksler, K. Wagner and B. D. Hammock
Affiliation:
Keywords:Cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 (CYP), soluble epoxide hydrolase (sEH), multitargetinhibitors, dual inhibitors
Abstract: Arachidonic acid (ARA) undergoes enzyme-mediated oxidative metabolism, resulting in the formation of anumber of biologically active metabolites. For over a century, these biochemical transformations have been the target ofnumerous pharmacological drugs for inflammation and pain. In particular, non-steroidal anti-inflammatory drugs(NSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors (coxibs) are widely used in the treatment of inflammationand pain. However, gastrointestinal (GI) and cardiovascular adverse effects of NSAIDs and coxibs, and recent findingsdemonstrating that there are significant risks from the disruption of oxylipin levels when pharmacologically inhibiting asingle ARA cascade metabolic pathway, have led to studies involving the simultaneous inhibition of multiple pathways inARA cascade. These studies suggest that multitarget inhibition represents a new and valuable option to enhance efficacyor reduce side-effects in the treatment of inflammation and pain. This review focuses on the crosstalk within the threepathways of the ARA cascade (cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450)), andsummarizes the current and future approaches of multitarget inhibitors for the treatment of eicosanoid driven inflammationand pain.
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Hwang S. H., Wecksler A. T., Wagner K. and Hammock B. D., Rationally Designed Multitarget Agents Against Inflammation and Pain, Current Medicinal Chemistry 2013; 20 (13) .https://dx.doi.org/10.2174/0929867311320130013
| DOI https://dx.doi.org/10.2174/0929867311320130013 | Print ISSN 0929-8673 |
| Publisher Name Bentham Science Publisher | Online ISSN 1875-533X |
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