Omega-3 Polyunsaturated Fatty Acid Derived Lipid Mediators and Their Application in Drug Discovery.

Pazderka, CW; Oliver, B; Murray, M; Rawling, T

Omega-3 Polyunsaturated Fatty Acid Derived Lipid Mediators and Their Application in Drug Discovery.

Pazderka, CW Oliver, B

Murray, M Rawling, T

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Publisher:: Bentham Science Publishers
Publication Type:: Journal Article
Citation:: Current Medicinal Chemistry, 2020, 27, (10), pp. 1670-1689
Issue Date:: 2020

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Field	Value	Language
dc.contributor.author	Pazderka, CW
dc.contributor.author	Oliver, B https://orcid.org/0000-0002-7122-9262
dc.contributor.author	Murray, M
dc.contributor.author	Rawling, T https://orcid.org/0000-0002-6624-6586
dc.date.accessioned	2021-03-09T04:04:54Z
dc.date.available	2018-08-27
dc.date.available	2021-03-09T04:04:54Z
dc.date.issued	2020
dc.identifier.citation	Current Medicinal Chemistry, 2020, 27, (10), pp. 1670-1689
dc.identifier.issn	0929-8673
dc.identifier.issn	1875-533X
dc.identifier.uri	http://hdl.handle.net/10453/146960
dc.description.abstract	Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play crucial and often opposing regulatory roles in health and in pathological conditions. n-3 and n-6 PUFA undergo biotransformation to parallel series of lipid mediators that are potent modulators of many cellular processes. A wide range of biological actions have been attributed to lipid mediators derived from n-6 PUFA, and these mediators have served as lead compounds in the development of numerous clinically approved drugs, including latanoprost (Xalatan: Pfizer), which is listed on the WHO Model List of Essential Medicines. n-3 PUFA-derived mediators have received less attention, in part because early studies suggested that n-3 PUFA act simply as competitive substrates for biotransformation enzymes and decrease the formation of n-6 PUFA-derived lipid mediators. However, more recent studies suggest that n-3 PUFA-derived mediators are biologically important in their own right. It is now emerging that many n-3 PUFA-derived lipid mediators have potent and diverse activities that are distinct from their n-6 counterparts. These findings provide new opportunities for drug discovery. Herein, we review the biosynthesis of n-3 PUFA-derived lipid mediators and highlight their biological actions that may be exploited for drug development. Lastly, we provide examples of medicinal chemistry research that has utilized n-3 PUFA-derived lipid mediators as novel lead compounds in drug design.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Bentham Science Publishers
dc.relation.ispartof	Current Medicinal Chemistry
dc.relation.isbasedon	10.2174/0929867325666180927100120
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	Medicinal & Biomolecular Chemistry
dc.subject.mesh	Fatty Acids, Omega-3
dc.subject.mesh	Drug Discovery
dc.subject.mesh	Drug Discovery
dc.subject.mesh	Fatty Acids, Omega-3
dc.title	Omega-3 Polyunsaturated Fatty Acid Derived Lipid Mediators and Their Application in Drug Discovery.
dc.type	Journal Article
utslib.citation.volume	27
utslib.location.activity	United Arab Emirates
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access	*
pubs.consider-herdc	true
dc.date.updated	2021-03-09T04:04:52Z
pubs.issue	10
pubs.publication-status	Published
pubs.volume	27
utslib.citation.issue	10

Abstract:

Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play crucial and often opposing regulatory roles in health and in pathological conditions. n-3 and n-6 PUFA undergo biotransformation to parallel series of lipid mediators that are potent modulators of many cellular processes. A wide range of biological actions have been attributed to lipid mediators derived from n-6 PUFA, and these mediators have served as lead compounds in the development of numerous clinically approved drugs, including latanoprost (Xalatan: Pfizer), which is listed on the WHO Model List of Essential Medicines. n-3 PUFA-derived mediators have received less attention, in part because early studies suggested that n-3 PUFA act simply as competitive substrates for biotransformation enzymes and decrease the formation of n-6 PUFA-derived lipid mediators. However, more recent studies suggest that n-3 PUFA-derived mediators are biologically important in their own right. It is now emerging that many n-3 PUFA-derived lipid mediators have potent and diverse activities that are distinct from their n-6 counterparts. These findings provide new opportunities for drug discovery. Herein, we review the biosynthesis of n-3 PUFA-derived lipid mediators and highlight their biological actions that may be exploited for drug development. Lastly, we provide examples of medicinal chemistry research that has utilized n-3 PUFA-derived lipid mediators as novel lead compounds in drug design.

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http://hdl.handle.net/10453/146960