Diclofenac Identified as a Kynurenine 3-Monooxygenase Binder and Inhibitor by Molecular Similarity Techniques

[Image: see text] In this study, we apply a battery of molecular similarity techniques to known inhibitors of kynurenine 3-monooxygenase (KMO), querying each against a repository of approved, experimental, nutraceutical, and illicit drugs. Four compounds are assayed against KMO. Subsequently, diclof...

Descripción completa

Detalles Bibliográficos
Autores principales: Shave, Steven, McGuire, Kris, Pham, Nhan T., Mole, Damian J., Webster, Scott P., Auer, Manfred
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044753/
https://www.ncbi.nlm.nih.gov/pubmed/30023839
http://dx.doi.org/10.1021/acsomega.7b02091
_version_ 1783339534208991232
author Shave, Steven
McGuire, Kris
Pham, Nhan T.
Mole, Damian J.
Webster, Scott P.
Auer, Manfred
author_facet Shave, Steven
McGuire, Kris
Pham, Nhan T.
Mole, Damian J.
Webster, Scott P.
Auer, Manfred
author_sort Shave, Steven
collection PubMed
description [Image: see text] In this study, we apply a battery of molecular similarity techniques to known inhibitors of kynurenine 3-monooxygenase (KMO), querying each against a repository of approved, experimental, nutraceutical, and illicit drugs. Four compounds are assayed against KMO. Subsequently, diclofenac (also known by the trade names Voltaren, Voltarol, Aclonac, and Cataflam) has been confirmed as a human KMO protein binder and inhibitor in cell lysate with low micromolar K(D) and IC(50), respectively, and low millimolar cellular IC(50). Hit to drug hopping, as exemplified here for one of the most successful anti-inflammatory medicines ever invented, holds great promise for expansion into new disease areas and highlights the not-yet-fully-exploited potential of drug repurposing.
format Online
Article
Text
id pubmed-6044753
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-60447532018-07-16 Diclofenac Identified as a Kynurenine 3-Monooxygenase Binder and Inhibitor by Molecular Similarity Techniques Shave, Steven McGuire, Kris Pham, Nhan T. Mole, Damian J. Webster, Scott P. Auer, Manfred ACS Omega [Image: see text] In this study, we apply a battery of molecular similarity techniques to known inhibitors of kynurenine 3-monooxygenase (KMO), querying each against a repository of approved, experimental, nutraceutical, and illicit drugs. Four compounds are assayed against KMO. Subsequently, diclofenac (also known by the trade names Voltaren, Voltarol, Aclonac, and Cataflam) has been confirmed as a human KMO protein binder and inhibitor in cell lysate with low micromolar K(D) and IC(50), respectively, and low millimolar cellular IC(50). Hit to drug hopping, as exemplified here for one of the most successful anti-inflammatory medicines ever invented, holds great promise for expansion into new disease areas and highlights the not-yet-fully-exploited potential of drug repurposing. American Chemical Society 2018-03-02 /pmc/articles/PMC6044753/ /pubmed/30023839 http://dx.doi.org/10.1021/acsomega.7b02091 Text en Copyright © 2018 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Shave, Steven
McGuire, Kris
Pham, Nhan T.
Mole, Damian J.
Webster, Scott P.
Auer, Manfred
Diclofenac Identified as a Kynurenine 3-Monooxygenase Binder and Inhibitor by Molecular Similarity Techniques
title Diclofenac Identified as a Kynurenine 3-Monooxygenase Binder and Inhibitor by Molecular Similarity Techniques
title_full Diclofenac Identified as a Kynurenine 3-Monooxygenase Binder and Inhibitor by Molecular Similarity Techniques
title_fullStr Diclofenac Identified as a Kynurenine 3-Monooxygenase Binder and Inhibitor by Molecular Similarity Techniques
title_full_unstemmed Diclofenac Identified as a Kynurenine 3-Monooxygenase Binder and Inhibitor by Molecular Similarity Techniques
title_short Diclofenac Identified as a Kynurenine 3-Monooxygenase Binder and Inhibitor by Molecular Similarity Techniques
title_sort diclofenac identified as a kynurenine 3-monooxygenase binder and inhibitor by molecular similarity techniques
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044753/
https://www.ncbi.nlm.nih.gov/pubmed/30023839
http://dx.doi.org/10.1021/acsomega.7b02091
work_keys_str_mv AT shavesteven diclofenacidentifiedasakynurenine3monooxygenasebinderandinhibitorbymolecularsimilaritytechniques
AT mcguirekris diclofenacidentifiedasakynurenine3monooxygenasebinderandinhibitorbymolecularsimilaritytechniques
AT phamnhant diclofenacidentifiedasakynurenine3monooxygenasebinderandinhibitorbymolecularsimilaritytechniques
AT moledamianj diclofenacidentifiedasakynurenine3monooxygenasebinderandinhibitorbymolecularsimilaritytechniques
AT websterscottp diclofenacidentifiedasakynurenine3monooxygenasebinderandinhibitorbymolecularsimilaritytechniques
AT auermanfred diclofenacidentifiedasakynurenine3monooxygenasebinderandinhibitorbymolecularsimilaritytechniques

Ejemplares similares