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

Abstract 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 cons...

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Autores principales:	Pascal Heitel, Leonie Gellrich, Jan Heering, Tamara Goebel, Astrid Kahnt, Ewgenij Proschak, Manfred Schubert-Zsilavecz, Daniel Merk
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/99894e9ac49c488b912c6cbbe9902276
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spelling	oai:doaj.org-article:99894e9ac49c488b912c6cbbe99022762021-12-02T15:08:37ZUrate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro10.1038/s41598-018-31833-42045-2322https://doaj.org/article/99894e9ac49c488b912c6cbbe99022762018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-31833-4https://doaj.org/toc/2045-2322Abstract 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).Pascal HeitelLeonie GellrichJan HeeringTamara GoebelAstrid KahntEwgenij ProschakManfred Schubert-ZsilaveczDaniel MerkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pascal Heitel Leonie Gellrich Jan Heering Tamara Goebel Astrid Kahnt Ewgenij Proschak Manfred Schubert-Zsilavecz Daniel Merk Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro
description	Abstract 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).
format	article
author	Pascal Heitel Leonie Gellrich Jan Heering Tamara Goebel Astrid Kahnt Ewgenij Proschak Manfred Schubert-Zsilavecz Daniel Merk
author_facet	Pascal Heitel Leonie Gellrich Jan Heering Tamara Goebel Astrid Kahnt Ewgenij Proschak Manfred Schubert-Zsilavecz Daniel Merk
author_sort	Pascal Heitel
title	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_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_sort	urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (spparγm) in vitro
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/99894e9ac49c488b912c6cbbe9902276
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Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro

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