Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a (1)H-NMR Method to Assess Deacetylase Activity

The search for potent and selective sirtuin inhibitors continues as chemical tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. These studies identify a sub...

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Autores principales: Pirrie, Lisa, McCarthy, Anna R., Major, Louise L., Morkūnaitė, Vaida, Zubrienė, Asta, Matulis, Daumantas, Lain, Sonia, Lebl, Tomas, Westwood, Nicholas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268290/
https://www.ncbi.nlm.nih.gov/pubmed/23079492
http://dx.doi.org/10.3390/molecules171012206
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author Pirrie, Lisa
McCarthy, Anna R.
Major, Louise L.
Morkūnaitė, Vaida
Zubrienė, Asta
Matulis, Daumantas
Lain, Sonia
Lebl, Tomas
Westwood, Nicholas J.
author_facet Pirrie, Lisa
McCarthy, Anna R.
Major, Louise L.
Morkūnaitė, Vaida
Zubrienė, Asta
Matulis, Daumantas
Lain, Sonia
Lebl, Tomas
Westwood, Nicholas J.
author_sort Pirrie, Lisa
collection PubMed
description The search for potent and selective sirtuin inhibitors continues as chemical tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. These studies identify a sub-micromolar inhibitor that has increased selectivity for SIRT2 over SIRT1 compared to tenovin-6. In addition, a (1)H-NMR-based method is developed and used to validate further this class of sirtuin inhibitors. A thermal shift analysis of SIRT2 in the presence of tenovin-6, -43, a control tenovin and the known SIRT2 inhibitor AGK2 is also presented.
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spelling pubmed-62682902018-12-12 Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a (1)H-NMR Method to Assess Deacetylase Activity Pirrie, Lisa McCarthy, Anna R. Major, Louise L. Morkūnaitė, Vaida Zubrienė, Asta Matulis, Daumantas Lain, Sonia Lebl, Tomas Westwood, Nicholas J. Molecules Article The search for potent and selective sirtuin inhibitors continues as chemical tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. These studies identify a sub-micromolar inhibitor that has increased selectivity for SIRT2 over SIRT1 compared to tenovin-6. In addition, a (1)H-NMR-based method is developed and used to validate further this class of sirtuin inhibitors. A thermal shift analysis of SIRT2 in the presence of tenovin-6, -43, a control tenovin and the known SIRT2 inhibitor AGK2 is also presented. MDPI 2012-10-18 /pmc/articles/PMC6268290/ /pubmed/23079492 http://dx.doi.org/10.3390/molecules171012206 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Pirrie, Lisa
McCarthy, Anna R.
Major, Louise L.
Morkūnaitė, Vaida
Zubrienė, Asta
Matulis, Daumantas
Lain, Sonia
Lebl, Tomas
Westwood, Nicholas J.
Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a (1)H-NMR Method to Assess Deacetylase Activity
title Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a (1)H-NMR Method to Assess Deacetylase Activity
title_full Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a (1)H-NMR Method to Assess Deacetylase Activity
title_fullStr Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a (1)H-NMR Method to Assess Deacetylase Activity
title_full_unstemmed Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a (1)H-NMR Method to Assess Deacetylase Activity
title_short Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a (1)H-NMR Method to Assess Deacetylase Activity
title_sort discovery and validation of sirt2 inhibitors based on tenovin-6: use of a (1)h-nmr method to assess deacetylase activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268290/
https://www.ncbi.nlm.nih.gov/pubmed/23079492
http://dx.doi.org/10.3390/molecules171012206
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