Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro

Gout is the most common arthritic disease in human but was long neglected and therapeutic options are not satisfying. However, with the recent approval of the urate transporter inhibitor lesinurad, gout treatment has experienced a major innovation. Here we show that lesinurad possesses considerable...

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Autores principales: Heitel, Pascal, Gellrich, Leonie, Heering, Jan, Goebel, Tamara, Kahnt, Astrid, Proschak, Ewgenij, Schubert-Zsilavecz, Manfred, Merk, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131501/
https://www.ncbi.nlm.nih.gov/pubmed/30202096
http://dx.doi.org/10.1038/s41598-018-31833-4
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author Heitel, Pascal
Gellrich, Leonie
Heering, Jan
Goebel, Tamara
Kahnt, Astrid
Proschak, Ewgenij
Schubert-Zsilavecz, Manfred
Merk, Daniel
author_facet Heitel, Pascal
Gellrich, Leonie
Heering, Jan
Goebel, Tamara
Kahnt, Astrid
Proschak, Ewgenij
Schubert-Zsilavecz, Manfred
Merk, Daniel
author_sort Heitel, Pascal
collection PubMed
description Gout is the most common arthritic disease in human but was long neglected and therapeutic options are not satisfying. However, with the recent approval of the urate transporter inhibitor lesinurad, gout treatment has experienced a major innovation. Here we show that lesinurad possesses considerable modulatory potency on peroxisome proliferator-activated receptor γ (PPARγ). Since gout has a strong association with metabolic diseases such as type 2 diabetes, this side-activity appears as very valuable contributing factor to the clinical efficacy profile of lesinurad. Importantly, despite robustly activating PPARγ in vitro, lesinurad lacked adipogenic activity, which seems due to differential coactivator recruitment and is characterized as selective PPARγ modulator (sPPARγM).
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spelling pubmed-61315012018-09-13 Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro Heitel, Pascal Gellrich, Leonie Heering, Jan Goebel, Tamara Kahnt, Astrid Proschak, Ewgenij Schubert-Zsilavecz, Manfred Merk, Daniel Sci Rep Article Gout is the most common arthritic disease in human but was long neglected and therapeutic options are not satisfying. However, with the recent approval of the urate transporter inhibitor lesinurad, gout treatment has experienced a major innovation. Here we show that lesinurad possesses considerable modulatory potency on peroxisome proliferator-activated receptor γ (PPARγ). Since gout has a strong association with metabolic diseases such as type 2 diabetes, this side-activity appears as very valuable contributing factor to the clinical efficacy profile of lesinurad. Importantly, despite robustly activating PPARγ in vitro, lesinurad lacked adipogenic activity, which seems due to differential coactivator recruitment and is characterized as selective PPARγ modulator (sPPARγM). Nature Publishing Group UK 2018-09-10 /pmc/articles/PMC6131501/ /pubmed/30202096 http://dx.doi.org/10.1038/s41598-018-31833-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Heitel, Pascal
Gellrich, Leonie
Heering, Jan
Goebel, Tamara
Kahnt, Astrid
Proschak, Ewgenij
Schubert-Zsilavecz, Manfred
Merk, Daniel
Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro
title Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro
title_full Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro
title_fullStr Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro
title_full_unstemmed Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro
title_short Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro
title_sort urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (spparγm) in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131501/
https://www.ncbi.nlm.nih.gov/pubmed/30202096
http://dx.doi.org/10.1038/s41598-018-31833-4
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