Design of negative and positive allosteric modulators of the cannabinoid CB2 Receptor derived from the natural product cannabidiol

Cannabidiol (CBD), the second most abundant of the active compounds found in the Cannabis sativa plant, is of increasing interest because it is approved for human use and is neither euphorizing nor addictive. Here, we design and synthesize novel compounds taking into account that CBD is both a parti...

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Autores: Navarro Brugal, Gemma|||0000-0003-4654-0873, Gonzalez, Angel|||0000-0002-2284-8307, Sánchez-Morales, Adrià|||0000-0002-8692-0988, Casajuana-Martin, Nil|||0000-0002-9007-274X, Gómez-Ventura, Marc, Cordomí Montoya, Arnau|||0000-0002-3848-2928, Busqué, Félix|||0000-0001-7566-4264, Alibés, Ramon|||0000-0002-7997-2691, Pardo Carrasco, Leonardo|||0000-0003-1778-7420, Franco, Rafael|||0000-0003-2549-4919
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:279275
Acceso en línea:https://ddd.uab.cat/record/279275
https://dx.doi.org/urn:doi:10.1021/acs.jmedchem.1c00561
Access Level:acceso abierto
Palabra clave:Agonists
Nicotinamide
Polyacrylamide
Receptors
Screening assays
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spelling Design of negative and positive allosteric modulators of the cannabinoid CB2 Receptor derived from the natural product cannabidiolNavarro Brugal, Gemma|||0000-0003-4654-0873Gonzalez, Angel|||0000-0002-2284-8307Sánchez-Morales, Adrià|||0000-0002-8692-0988Casajuana-Martin, Nil|||0000-0002-9007-274XGómez-Ventura, MarcCordomí Montoya, Arnau|||0000-0002-3848-2928Busqué, Félix|||0000-0001-7566-4264Alibés, Ramon|||0000-0002-7997-2691Pardo Carrasco, Leonardo|||0000-0003-1778-7420Franco, Rafael|||0000-0003-2549-4919AgonistsNicotinamidePolyacrylamideReceptorsScreening assaysCannabidiol (CBD), the second most abundant of the active compounds found in the Cannabis sativa plant, is of increasing interest because it is approved for human use and is neither euphorizing nor addictive. Here, we design and synthesize novel compounds taking into account that CBD is both a partial agonist, when it binds to the orthosteric site, and a negative allosteric modulator, when it binds to the allosteric site of the cannabinoid CB2 receptor. Molecular dynamic simulations and site-directed mutagenesis studies have identified the allosteric site near the receptor entrance. This knowledge has permitted to perform structure-guided design of negative and positive allosteric modulators of the CB2 receptor with potential therapeutic utility. 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/279275https://dx.doi.org/urn:doi:10.1021/acs.jmedchem.1c00561reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2017-84117-RAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-098830-B-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-106403RB-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-109240RB-I00open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2792752026-06-06T12:50:31Z
dc.title.none.fl_str_mv Design of negative and positive allosteric modulators of the cannabinoid CB2 Receptor derived from the natural product cannabidiol
title Design of negative and positive allosteric modulators of the cannabinoid CB2 Receptor derived from the natural product cannabidiol
spellingShingle Design of negative and positive allosteric modulators of the cannabinoid CB2 Receptor derived from the natural product cannabidiol
Navarro Brugal, Gemma|||0000-0003-4654-0873
Agonists
Nicotinamide
Polyacrylamide
Receptors
Screening assays
title_short Design of negative and positive allosteric modulators of the cannabinoid CB2 Receptor derived from the natural product cannabidiol
title_full Design of negative and positive allosteric modulators of the cannabinoid CB2 Receptor derived from the natural product cannabidiol
title_fullStr Design of negative and positive allosteric modulators of the cannabinoid CB2 Receptor derived from the natural product cannabidiol
title_full_unstemmed Design of negative and positive allosteric modulators of the cannabinoid CB2 Receptor derived from the natural product cannabidiol
title_sort Design of negative and positive allosteric modulators of the cannabinoid CB2 Receptor derived from the natural product cannabidiol
dc.creator.none.fl_str_mv Navarro Brugal, Gemma|||0000-0003-4654-0873
Gonzalez, Angel|||0000-0002-2284-8307
Sánchez-Morales, Adrià|||0000-0002-8692-0988
Casajuana-Martin, Nil|||0000-0002-9007-274X
Gómez-Ventura, Marc
Cordomí Montoya, Arnau|||0000-0002-3848-2928
Busqué, Félix|||0000-0001-7566-4264
Alibés, Ramon|||0000-0002-7997-2691
Pardo Carrasco, Leonardo|||0000-0003-1778-7420
Franco, Rafael|||0000-0003-2549-4919
author Navarro Brugal, Gemma|||0000-0003-4654-0873
author_facet Navarro Brugal, Gemma|||0000-0003-4654-0873
Gonzalez, Angel|||0000-0002-2284-8307
Sánchez-Morales, Adrià|||0000-0002-8692-0988
Casajuana-Martin, Nil|||0000-0002-9007-274X
Gómez-Ventura, Marc
Cordomí Montoya, Arnau|||0000-0002-3848-2928
Busqué, Félix|||0000-0001-7566-4264
Alibés, Ramon|||0000-0002-7997-2691
Pardo Carrasco, Leonardo|||0000-0003-1778-7420
Franco, Rafael|||0000-0003-2549-4919
author_role author
author2 Gonzalez, Angel|||0000-0002-2284-8307
Sánchez-Morales, Adrià|||0000-0002-8692-0988
Casajuana-Martin, Nil|||0000-0002-9007-274X
Gómez-Ventura, Marc
Cordomí Montoya, Arnau|||0000-0002-3848-2928
Busqué, Félix|||0000-0001-7566-4264
Alibés, Ramon|||0000-0002-7997-2691
Pardo Carrasco, Leonardo|||0000-0003-1778-7420
Franco, Rafael|||0000-0003-2549-4919
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Agonists
Nicotinamide
Polyacrylamide
Receptors
Screening assays
topic Agonists
Nicotinamide
Polyacrylamide
Receptors
Screening assays
description Cannabidiol (CBD), the second most abundant of the active compounds found in the Cannabis sativa plant, is of increasing interest because it is approved for human use and is neither euphorizing nor addictive. Here, we design and synthesize novel compounds taking into account that CBD is both a partial agonist, when it binds to the orthosteric site, and a negative allosteric modulator, when it binds to the allosteric site of the cannabinoid CB2 receptor. Molecular dynamic simulations and site-directed mutagenesis studies have identified the allosteric site near the receptor entrance. This knowledge has permitted to perform structure-guided design of negative and positive allosteric modulators of the CB2 receptor with potential therapeutic utility.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/279275
https://dx.doi.org/urn:doi:10.1021/acs.jmedchem.1c00561
url https://ddd.uab.cat/record/279275
https://dx.doi.org/urn:doi:10.1021/acs.jmedchem.1c00561
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2017-84117-R
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-098830-B-I00
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-106403RB-I00
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-109240RB-I00
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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