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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-8747024 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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