Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition

Kennedy et al. report the pharmacological and in vivo profiling of two small molecule PAR2 inhibitors and an agonist. They conclude that while the small molecule agonist and one of the inhibitors bind to the orthosteric PAR2 binding site, the other inhibitor is a negative allosteric modulator, highl...

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Autores principales:	Amanda J. Kennedy, Linda Sundström, Stefan Geschwindner, Eunice K. Y. Poon, Yuhong Jiang, Rongfeng Chen, Rob Cooke, Shawn Johnstone, Andrew Madin, Junxian Lim, Qingqi Liu, Rink-Jan Lohman, Anneli Nordqvist, Maria Fridén-Saxin, Wenzhen Yang, Dean G. Brown, David P. Fairlie, Niek Dekker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e6a39fb1480d47f3b76e5e7e14d4b26c
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spelling	oai:doaj.org-article:e6a39fb1480d47f3b76e5e7e14d4b26c2021-12-02T11:57:54ZProtease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition10.1038/s42003-020-01504-02399-3642https://doaj.org/article/e6a39fb1480d47f3b76e5e7e14d4b26c2020-12-01T00:00:00Zhttps://doi.org/10.1038/s42003-020-01504-0https://doaj.org/toc/2399-3642Kennedy et al. report the pharmacological and in vivo profiling of two small molecule PAR2 inhibitors and an agonist. They conclude that while the small molecule agonist and one of the inhibitors bind to the orthosteric PAR2 binding site, the other inhibitor is a negative allosteric modulator, highlighting two distinct mechanisms of inhibition that could be targeted for future development of drugs that modulate PAR2.Amanda J. KennedyLinda SundströmStefan GeschwindnerEunice K. Y. PoonYuhong JiangRongfeng ChenRob CookeShawn JohnstoneAndrew MadinJunxian LimQingqi LiuRink-Jan LohmanAnneli NordqvistMaria Fridén-SaxinWenzhen YangDean G. BrownDavid P. FairlieNiek DekkerNature PortfolioarticleBiology (General)QH301-705.5ENCommunications Biology, Vol 3, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Amanda J. Kennedy Linda Sundström Stefan Geschwindner Eunice K. Y. Poon Yuhong Jiang Rongfeng Chen Rob Cooke Shawn Johnstone Andrew Madin Junxian Lim Qingqi Liu Rink-Jan Lohman Anneli Nordqvist Maria Fridén-Saxin Wenzhen Yang Dean G. Brown David P. Fairlie Niek Dekker Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition
description	Kennedy et al. report the pharmacological and in vivo profiling of two small molecule PAR2 inhibitors and an agonist. They conclude that while the small molecule agonist and one of the inhibitors bind to the orthosteric PAR2 binding site, the other inhibitor is a negative allosteric modulator, highlighting two distinct mechanisms of inhibition that could be targeted for future development of drugs that modulate PAR2.
format	article
author	Amanda J. Kennedy Linda Sundström Stefan Geschwindner Eunice K. Y. Poon Yuhong Jiang Rongfeng Chen Rob Cooke Shawn Johnstone Andrew Madin Junxian Lim Qingqi Liu Rink-Jan Lohman Anneli Nordqvist Maria Fridén-Saxin Wenzhen Yang Dean G. Brown David P. Fairlie Niek Dekker
author_facet	Amanda J. Kennedy Linda Sundström Stefan Geschwindner Eunice K. Y. Poon Yuhong Jiang Rongfeng Chen Rob Cooke Shawn Johnstone Andrew Madin Junxian Lim Qingqi Liu Rink-Jan Lohman Anneli Nordqvist Maria Fridén-Saxin Wenzhen Yang Dean G. Brown David P. Fairlie Niek Dekker
author_sort	Amanda J. Kennedy
title	Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition
title_short	Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition
title_full	Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition
title_fullStr	Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition
title_full_unstemmed	Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition
title_sort	protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e6a39fb1480d47f3b76e5e7e14d4b26c
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Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition

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