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The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors

Under normal physiological conditions, the kynurenine pathway (KP) plays a critical role in generating cellular energy and catabolizing tryptophan. Under inflammatory conditions, however, there is an upregulation of the KP enzymes, particularly kynurenine 3-monooxygenase (KMO). KMO has garnered much...

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Autores principales: Hughes, Tamera D., Güner, Osman F., Iradukunda, Emma Carine, Phillips, Robert S., Bowen, J. Phillip
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747024/
https://www.ncbi.nlm.nih.gov/pubmed/35011505
http://dx.doi.org/10.3390/molecules27010273
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author Hughes, Tamera D.
Güner, Osman F.
Iradukunda, Emma Carine
Phillips, Robert S.
Bowen, J. Phillip
author_facet Hughes, Tamera D.
Güner, Osman F.
Iradukunda, Emma Carine
Phillips, Robert S.
Bowen, J. Phillip
author_sort Hughes, Tamera D.
collection PubMed
description Under normal physiological conditions, the kynurenine pathway (KP) plays a critical role in generating cellular energy and catabolizing tryptophan. Under inflammatory conditions, however, there is an upregulation of the KP enzymes, particularly kynurenine 3-monooxygenase (KMO). KMO has garnered much attention due to its production of toxic metabolites that have been implicated in many diseases and disorders. With many of these illnesses having an inadequate or modest treatment, there exists a need to develop KMO inhibitors that reduce the production of these toxic metabolites. Though prior efforts to find an appropriate KMO inhibitor were unpromising, the development of a KMO crystal structure has provided the opportunity for a rational structure-based design in the development of inhibitors. Therefore, the purpose of this review is to describe the kynurenine pathway, the kynurenine 3-monooxygenase enzyme, and KMO inhibitors and their potential candidacy for clinical use.
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spelling pubmed-87470242022-01-11 The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors Hughes, Tamera D. Güner, Osman F. Iradukunda, Emma Carine Phillips, Robert S. Bowen, J. Phillip Molecules Review Under normal physiological conditions, the kynurenine pathway (KP) plays a critical role in generating cellular energy and catabolizing tryptophan. Under inflammatory conditions, however, there is an upregulation of the KP enzymes, particularly kynurenine 3-monooxygenase (KMO). KMO has garnered much attention due to its production of toxic metabolites that have been implicated in many diseases and disorders. With many of these illnesses having an inadequate or modest treatment, there exists a need to develop KMO inhibitors that reduce the production of these toxic metabolites. Though prior efforts to find an appropriate KMO inhibitor were unpromising, the development of a KMO crystal structure has provided the opportunity for a rational structure-based design in the development of inhibitors. Therefore, the purpose of this review is to describe the kynurenine pathway, the kynurenine 3-monooxygenase enzyme, and KMO inhibitors and their potential candidacy for clinical use. MDPI 2022-01-02 /pmc/articles/PMC8747024/ /pubmed/35011505 http://dx.doi.org/10.3390/molecules27010273 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hughes, Tamera D.
Güner, Osman F.
Iradukunda, Emma Carine
Phillips, Robert S.
Bowen, J. Phillip
The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors
title The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors
title_full The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors
title_fullStr The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors
title_full_unstemmed The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors
title_short The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors
title_sort kynurenine pathway and kynurenine 3-monooxygenase inhibitors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747024/
https://www.ncbi.nlm.nih.gov/pubmed/35011505
http://dx.doi.org/10.3390/molecules27010273
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