Identification of new target proteins of a Urotensin-II receptor antagonist using transcriptome-based drug repositioning approach

Abstract Drug repositioning research using transcriptome data has recently attracted attention. In this study, we attempted to identify new target proteins of the urotensin-II receptor antagonist, KR-37524 (4-(3-bromo-4-(piperidin-4-yloxy)benzyl)-N-(3-(dimethylamino)phenyl)piperazine-1-carboxamide d...

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Autores principales:	Gyutae Lim, Chae Jo Lim, Jeong Hyun Lee, Byung Ho Lee, Jae Yong Ryu, Kwang-Seok Oh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5e79377f13c34e84b8825e436aafd9b7
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spelling	oai:doaj.org-article:5e79377f13c34e84b8825e436aafd9b72021-12-02T15:09:23ZIdentification of new target proteins of a Urotensin-II receptor antagonist using transcriptome-based drug repositioning approach10.1038/s41598-021-96612-02045-2322https://doaj.org/article/5e79377f13c34e84b8825e436aafd9b72021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96612-0https://doaj.org/toc/2045-2322Abstract Drug repositioning research using transcriptome data has recently attracted attention. In this study, we attempted to identify new target proteins of the urotensin-II receptor antagonist, KR-37524 (4-(3-bromo-4-(piperidin-4-yloxy)benzyl)-N-(3-(dimethylamino)phenyl)piperazine-1-carboxamide dihydrochloride), using a transcriptome-based drug repositioning approach. To do this, we obtained KR-37524-induced gene expression profile changes in four cell lines (A375, A549, MCF7, and PC3), and compared them with the approved drug-induced gene expression profile changes available in the LINCS L1000 database to identify approved drugs with similar gene expression profile changes. Here, the similarity between the two gene expression profile changes was calculated using the connectivity score. We then selected proteins that are known targets of the top three approved drugs with the highest connectivity score in each cell line (12 drugs in total) as potential targets of KR-37524. Seven potential target proteins were experimentally confirmed using an in vitro binding assay. Through this analysis, we identified that neurologically regulated serotonin transporter proteins are new target proteins of KR-37524. These results indicate that the transcriptome-based drug repositioning approach can be used to identify new target proteins of a given compound, and we provide a standalone software developed in this study that will serve as a useful tool for drug repositioning.Gyutae LimChae Jo LimJeong Hyun LeeByung Ho LeeJae Yong RyuKwang-Seok OhNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gyutae Lim Chae Jo Lim Jeong Hyun Lee Byung Ho Lee Jae Yong Ryu Kwang-Seok Oh Identification of new target proteins of a Urotensin-II receptor antagonist using transcriptome-based drug repositioning approach
description	Abstract Drug repositioning research using transcriptome data has recently attracted attention. In this study, we attempted to identify new target proteins of the urotensin-II receptor antagonist, KR-37524 (4-(3-bromo-4-(piperidin-4-yloxy)benzyl)-N-(3-(dimethylamino)phenyl)piperazine-1-carboxamide dihydrochloride), using a transcriptome-based drug repositioning approach. To do this, we obtained KR-37524-induced gene expression profile changes in four cell lines (A375, A549, MCF7, and PC3), and compared them with the approved drug-induced gene expression profile changes available in the LINCS L1000 database to identify approved drugs with similar gene expression profile changes. Here, the similarity between the two gene expression profile changes was calculated using the connectivity score. We then selected proteins that are known targets of the top three approved drugs with the highest connectivity score in each cell line (12 drugs in total) as potential targets of KR-37524. Seven potential target proteins were experimentally confirmed using an in vitro binding assay. Through this analysis, we identified that neurologically regulated serotonin transporter proteins are new target proteins of KR-37524. These results indicate that the transcriptome-based drug repositioning approach can be used to identify new target proteins of a given compound, and we provide a standalone software developed in this study that will serve as a useful tool for drug repositioning.
format	article
author	Gyutae Lim Chae Jo Lim Jeong Hyun Lee Byung Ho Lee Jae Yong Ryu Kwang-Seok Oh
author_facet	Gyutae Lim Chae Jo Lim Jeong Hyun Lee Byung Ho Lee Jae Yong Ryu Kwang-Seok Oh
author_sort	Gyutae Lim
title	Identification of new target proteins of a Urotensin-II receptor antagonist using transcriptome-based drug repositioning approach
title_short	Identification of new target proteins of a Urotensin-II receptor antagonist using transcriptome-based drug repositioning approach
title_full	Identification of new target proteins of a Urotensin-II receptor antagonist using transcriptome-based drug repositioning approach
title_fullStr	Identification of new target proteins of a Urotensin-II receptor antagonist using transcriptome-based drug repositioning approach
title_full_unstemmed	Identification of new target proteins of a Urotensin-II receptor antagonist using transcriptome-based drug repositioning approach
title_sort	identification of new target proteins of a urotensin-ii receptor antagonist using transcriptome-based drug repositioning approach
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5e79377f13c34e84b8825e436aafd9b7
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Identification of new target proteins of a Urotensin-II receptor antagonist using transcriptome-based drug repositioning approach

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