Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids

Opioids are the most effective painkillers, but their benefit-risk balance often hinder their therapeutic use. WLB-73502 is a dual, bispecific compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. WLB-73502 is an antagonist at the S1R. It behaved as a partial MOR agonist at the G-protein...

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Detalhes bibliográficos
Autores: Vidal-Torres, Alba, Fernandez Pastor, Begoña, García López, Mónica, Ayet Galcerà, Eva, Cabot, Anna, Burgueño, Javier, Monroy, Xavier, Aubel, Bertrand, Codony, Xavier, Romero, Luz, Pascual, Rosalía, Serafini, MªTeresa, Encina, Gregorio, Almansa, Carmen, Zamanillo, Daniel, Merlos, Manuel, Vela, José Miguel
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:TecnoCampus
Repositorio:Repositori Digital del TecnoCampus
OAI Identifier:oai:repositori.tecnocampus.cat:20.500.12367/2877
Acesso em linha:http://hdl.handle.net/20.500.12367/2877
Access Level:acceso abierto
Palavra-chave:WLB-73502
Sigma-1 receptor
Mu-opioid receptor
Biased agonist
Analgesic activity
Chronic pain
Neuropathic pain
Safety
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oai_identifier_str oai:repositori.tecnocampus.cat:20.500.12367/2877
network_acronym_str ES
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repository_id_str
spelling Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioidsVidal-Torres, AlbaFernandez Pastor, BegoñaGarcía López, MónicaAyet Galcerà, EvaCabot, AnnaBurgueño, JavierMonroy, XavierAubel, BertrandCodony, XavierRomero, LuzPascual, RosalíaSerafini, MªTeresaEncina, GregorioAlmansa, CarmenZamanillo, DanielMerlos, ManuelVela, José MiguelWLB-73502Sigma-1 receptorMu-opioid receptorBiased agonistAnalgesic activityChronic painNeuropathic painSafetyOpioids are the most effective painkillers, but their benefit-risk balance often hinder their therapeutic use. WLB-73502 is a dual, bispecific compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. WLB-73502 is an antagonist at the S1R. It behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificant β-arrestin-2 recruitment, thus demonstrating low intrinsic efficacy on MOR at both signalling pathways. Despite its partial MOR agonism, WLB-73502 exerted full antinociceptive efficacy, with potency superior to morphine and similar to oxycodone against nociceptive, inflammatory and osteoarthritis pain, and superior to both morphine and oxycodone against neuropathic pain. [...]info:eu-repo/semantics/publishedVersionElsevier202520252023info:eu-repo/semantics/article18 p.application/pdfhttp://hdl.handle.net/20.500.12367/2877reponame:Repositori Digital del TecnoCampusinstname:TecnoCampusInglésActa Pharmaceutica Sinica B. 2023;13(1):82-99Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositori.tecnocampus.cat:20.500.12367/28772026-06-21T13:30:27Z
dc.title.none.fl_str_mv Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids
title Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids
spellingShingle Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids
Vidal-Torres, Alba
WLB-73502
Sigma-1 receptor
Mu-opioid receptor
Biased agonist
Analgesic activity
Chronic pain
Neuropathic pain
Safety
title_short Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids
title_full Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids
title_fullStr Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids
title_full_unstemmed Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids
title_sort Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids
dc.creator.none.fl_str_mv Vidal-Torres, Alba
Fernandez Pastor, Begoña
García López, Mónica
Ayet Galcerà, Eva
Cabot, Anna
Burgueño, Javier
Monroy, Xavier
Aubel, Bertrand
Codony, Xavier
Romero, Luz
Pascual, Rosalía
Serafini, MªTeresa
Encina, Gregorio
Almansa, Carmen
Zamanillo, Daniel
Merlos, Manuel
Vela, José Miguel
author Vidal-Torres, Alba
author_facet Vidal-Torres, Alba
Fernandez Pastor, Begoña
García López, Mónica
Ayet Galcerà, Eva
Cabot, Anna
Burgueño, Javier
Monroy, Xavier
Aubel, Bertrand
Codony, Xavier
Romero, Luz
Pascual, Rosalía
Serafini, MªTeresa
Encina, Gregorio
Almansa, Carmen
Zamanillo, Daniel
Merlos, Manuel
Vela, José Miguel
author_role author
author2 Fernandez Pastor, Begoña
García López, Mónica
Ayet Galcerà, Eva
Cabot, Anna
Burgueño, Javier
Monroy, Xavier
Aubel, Bertrand
Codony, Xavier
Romero, Luz
Pascual, Rosalía
Serafini, MªTeresa
Encina, Gregorio
Almansa, Carmen
Zamanillo, Daniel
Merlos, Manuel
Vela, José Miguel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv WLB-73502
Sigma-1 receptor
Mu-opioid receptor
Biased agonist
Analgesic activity
Chronic pain
Neuropathic pain
Safety
topic WLB-73502
Sigma-1 receptor
Mu-opioid receptor
Biased agonist
Analgesic activity
Chronic pain
Neuropathic pain
Safety
description Opioids are the most effective painkillers, but their benefit-risk balance often hinder their therapeutic use. WLB-73502 is a dual, bispecific compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. WLB-73502 is an antagonist at the S1R. It behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificant β-arrestin-2 recruitment, thus demonstrating low intrinsic efficacy on MOR at both signalling pathways. Despite its partial MOR agonism, WLB-73502 exerted full antinociceptive efficacy, with potency superior to morphine and similar to oxycodone against nociceptive, inflammatory and osteoarthritis pain, and superior to both morphine and oxycodone against neuropathic pain. [...]
publishDate 2023
dc.date.none.fl_str_mv 2023
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12367/2877
url http://hdl.handle.net/20.500.12367/2877
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Acta Pharmaceutica Sinica B. 2023;13(1):82-99
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 18 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositori Digital del TecnoCampus
instname:TecnoCampus
instname_str TecnoCampus
reponame_str Repositori Digital del TecnoCampus
collection Repositori Digital del TecnoCampus
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869402528739753984
score 15,812429

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