Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators

Both metabotropic (CBRs) and ionotropic cannabinoid receptors (ICRs) have implications in a range of neurological disorders. The metabotropic canonical CBRs CB1 and CB2 are highly implicated in these pathological events. However, selective targeting at CB2 versus CB1 offers optimized pharmacology du...

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Detalles Bibliográficos
Autores: Morales, Paula, Muller, Chanté, Jagerovic, Nadine, Reggio, Patricia H.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/333553
Acceso en línea:http://hdl.handle.net/10261/333553
Access Level:acceso abierto
Palabra clave:cannabinoids, ionotropic receptors, CB2, TRPV1, dual ligands, multitargeting
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spelling Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual ModulatorsMorales, PaulaMuller, ChantéJagerovic, NadineReggio, Patricia H.cannabinoids, ionotropic receptors, CB2, TRPV1, dual ligands, multitargetingBoth metabotropic (CBRs) and ionotropic cannabinoid receptors (ICRs) have implications in a range of neurological disorders. The metabotropic canonical CBRs CB1 and CB2 are highly implicated in these pathological events. However, selective targeting at CB2 versus CB1 offers optimized pharmacology due to the absence of psychoactive outcomes. The ICR transient receptor potential vanilloid type 1 (TRPV1) has also been reported to play a role in CNS disorders. Thus, activation of both targets, CB2 and TRPV1, offers a promising polypharmacological strategy for the treatment of neurological events including analgesia and neuroprotection. This brief research report aims to identify chemotypes with a potential dual CB2/TRPV1 profile. For this purpose, we have rationalized key structural features for activation and performed virtual screening at both targets using curated chemical libraries.This research was funded by the Spanish Ministry of Science and Innovation, grant number MICIU/FEDER: RTI 2018-095544-B-I00 and the Spanish National Research Council (CSIC), grant number PIE-201580E033, and the National Institute on Drug Abuse grant R01 DA003934 (PR) and F31 DA53022 (CM).Peer reviewedFrontiers MediaMinisterio de Ciencia e Innovación (España)Consejo Superior de Investigaciones Científicas (España)National Institute on Drug Abuse (US)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320222023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/333553reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-095544-B-I00http://dx.doi.org/10.3389/fmolb.2022.841190Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3335532026-05-22T06:33:51Z
dc.title.none.fl_str_mv Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators
title Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators
spellingShingle Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators
Morales, Paula
cannabinoids, ionotropic receptors, CB2, TRPV1, dual ligands, multitargeting
title_short Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators
title_full Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators
title_fullStr Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators
title_full_unstemmed Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators
title_sort Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators
dc.creator.none.fl_str_mv Morales, Paula
Muller, Chanté
Jagerovic, Nadine
Reggio, Patricia H.
author Morales, Paula
author_facet Morales, Paula
Muller, Chanté
Jagerovic, Nadine
Reggio, Patricia H.
author_role author
author2 Muller, Chanté
Jagerovic, Nadine
Reggio, Patricia H.
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Consejo Superior de Investigaciones Científicas (España)
National Institute on Drug Abuse (US)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv cannabinoids, ionotropic receptors, CB2, TRPV1, dual ligands, multitargeting
topic cannabinoids, ionotropic receptors, CB2, TRPV1, dual ligands, multitargeting
description Both metabotropic (CBRs) and ionotropic cannabinoid receptors (ICRs) have implications in a range of neurological disorders. The metabotropic canonical CBRs CB1 and CB2 are highly implicated in these pathological events. However, selective targeting at CB2 versus CB1 offers optimized pharmacology due to the absence of psychoactive outcomes. The ICR transient receptor potential vanilloid type 1 (TRPV1) has also been reported to play a role in CNS disorders. Thus, activation of both targets, CB2 and TRPV1, offers a promising polypharmacological strategy for the treatment of neurological events including analgesia and neuroprotection. This brief research report aims to identify chemotypes with a potential dual CB2/TRPV1 profile. For this purpose, we have rationalized key structural features for activation and performed virtual screening at both targets using curated chemical libraries.
publishDate 2022
dc.date.none.fl_str_mv 2022
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/10261/333553
url http://hdl.handle.net/10261/333553
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #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
http://dx.doi.org/10.3389/fmolb.2022.841190
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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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