Thienopyrimidine Derivatives as GPR55 Receptor Antagonists: Insight into Structure-Activity Relationship

GPR55 is an orphan G-protein coupled receptor involved in various pathophysiological conditions. However, there are only a few noncannabinoid GPR55 ligands reported so far. The lack of potent and selective GPR55 ligands precludes a deep exploration of this receptor. The studies presented here focuse...

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Autores: Figuerola-Asencio, Laura, Morales, Paula, Zhao, Pingwei, Hurst, D. P., Sayed, Sommayah S., Colón, Katsuya L., Gómez-Cañas, María, Fernández-Ruiz, Javier, Croatt, Mitchell P., Reggio, Patricia H., Abood, Mary E., Jagerovic, Nadine
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/309060
Acceso en línea:http://hdl.handle.net/10261/309060
Access Level:acceso abierto
Palabra clave:GPR55, antagonist, cannabinoid, thienopyrimidine, SAR
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spelling Thienopyrimidine Derivatives as GPR55 Receptor Antagonists: Insight into Structure-Activity RelationshipFiguerola-Asencio, LauraMorales, PaulaZhao, PingweiHurst, D. P.Sayed, Sommayah S.Colón, Katsuya L.Gómez-Cañas, MaríaFernández-Ruiz, JavierCroatt, Mitchell P.Reggio, Patricia H.Abood, Mary E.Jagerovic, NadineGPR55, antagonist, cannabinoid, thienopyrimidine, SARGPR55 is an orphan G-protein coupled receptor involved in various pathophysiological conditions. However, there are only a few noncannabinoid GPR55 ligands reported so far. The lack of potent and selective GPR55 ligands precludes a deep exploration of this receptor. The studies presented here focused on a thienopyrimidine scaffold based on the GPR55 antagonist ML192, previously discovered by high-throughput screening. The GPR55 activities of the new synthesized compounds were assessed using β-arrestin recruitment assays in Chinese hamster ovary cells overexpressing human GPR55. Some derivatives were identified as GPR55 antagonists with functional efficacy and selectivity versus CB1 and CB2 cannabinoid receptors.M.E.A., P.H.R., and N.J. are supported by National Institutes of Health grant R01 DA0455698. M.E.A. and P.Z. thank the financial support NIH P30 DA013429. P.M. and N.J. are supported by the Ministry of Science, Innovation, and Universities, Spain (MCIU)/FEDER grant RTI2018-095544-B-I00 and the Spanish National Research Council (CSIC) grant PIE-201580E033. P.M. acknowledges the Comunidad de Madrid (CM) programme “Atraccion de Talento” number 2018-T2/BMD-10819 and “Juan de la Cierva Incorporación Programme-MICIU” (IJC 2019-042182-I)Peer reviewedAmerican Chemical SocietyMinisterio de Ciencia, Innovación y Universidades (España)Consejo Superior de Investigaciones Científicas (España)Comunidad de MadridConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320232023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/309060reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-095544-B-I00S2018-T2/BMD-10819info:eu-repo/grantAgreement/AEI//IJC 2019-042182-Ihttp://dx.doi.org/10.1021/acsmedchemlett.2c00325Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3090602026-05-22T06:33:51Z
dc.title.none.fl_str_mv Thienopyrimidine Derivatives as GPR55 Receptor Antagonists: Insight into Structure-Activity Relationship
title Thienopyrimidine Derivatives as GPR55 Receptor Antagonists: Insight into Structure-Activity Relationship
spellingShingle Thienopyrimidine Derivatives as GPR55 Receptor Antagonists: Insight into Structure-Activity Relationship
Figuerola-Asencio, Laura
GPR55, antagonist, cannabinoid, thienopyrimidine, SAR
title_short Thienopyrimidine Derivatives as GPR55 Receptor Antagonists: Insight into Structure-Activity Relationship
title_full Thienopyrimidine Derivatives as GPR55 Receptor Antagonists: Insight into Structure-Activity Relationship
title_fullStr Thienopyrimidine Derivatives as GPR55 Receptor Antagonists: Insight into Structure-Activity Relationship
title_full_unstemmed Thienopyrimidine Derivatives as GPR55 Receptor Antagonists: Insight into Structure-Activity Relationship
title_sort Thienopyrimidine Derivatives as GPR55 Receptor Antagonists: Insight into Structure-Activity Relationship
dc.creator.none.fl_str_mv Figuerola-Asencio, Laura
Morales, Paula
Zhao, Pingwei
Hurst, D. P.
Sayed, Sommayah S.
Colón, Katsuya L.
Gómez-Cañas, María
Fernández-Ruiz, Javier
Croatt, Mitchell P.
Reggio, Patricia H.
Abood, Mary E.
Jagerovic, Nadine
author Figuerola-Asencio, Laura
author_facet Figuerola-Asencio, Laura
Morales, Paula
Zhao, Pingwei
Hurst, D. P.
Sayed, Sommayah S.
Colón, Katsuya L.
Gómez-Cañas, María
Fernández-Ruiz, Javier
Croatt, Mitchell P.
Reggio, Patricia H.
Abood, Mary E.
Jagerovic, Nadine
author_role author
author2 Morales, Paula
Zhao, Pingwei
Hurst, D. P.
Sayed, Sommayah S.
Colón, Katsuya L.
Gómez-Cañas, María
Fernández-Ruiz, Javier
Croatt, Mitchell P.
Reggio, Patricia H.
Abood, Mary E.
Jagerovic, Nadine
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Consejo Superior de Investigaciones Científicas (España)
Comunidad de Madrid
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv GPR55, antagonist, cannabinoid, thienopyrimidine, SAR
topic GPR55, antagonist, cannabinoid, thienopyrimidine, SAR
description GPR55 is an orphan G-protein coupled receptor involved in various pathophysiological conditions. However, there are only a few noncannabinoid GPR55 ligands reported so far. The lack of potent and selective GPR55 ligands precludes a deep exploration of this receptor. The studies presented here focused on a thienopyrimidine scaffold based on the GPR55 antagonist ML192, previously discovered by high-throughput screening. The GPR55 activities of the new synthesized compounds were assessed using β-arrestin recruitment assays in Chinese hamster ovary cells overexpressing human GPR55. Some derivatives were identified as GPR55 antagonists with functional efficacy and selectivity versus CB1 and CB2 cannabinoid receptors.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/309060
url http://hdl.handle.net/10261/309060
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-095544-B-I00
S2018-T2/BMD-10819
info:eu-repo/grantAgreement/AEI//IJC 2019-042182-I
http://dx.doi.org/10.1021/acsmedchemlett.2c00325
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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