2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.

García-Cárceles, Javier; Vázquez-Villa, Henar; Brea, José; Ladron de Guevara-Miranda, David; Cincilla, Giovanni; Sánchez-Martínez, Melchor; Sánchez-Merino, Anabel; Algar, Sergio; Teresa de Los Frailes, María; Roberts, Richard S; Ballesteros, Juan A; Rodríguez de Fonseca, Fernando; Benhamú, Bellinda; Loza, María I; López-Rodríguez, María L

2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.

Tolerance development caused by dopamine replacement with l-DOPA and therapeutic drawbacks upon activation of dopaminergic receptors with orthosteric agonists reveal a significant unmet need for safe and effective treatment of Parkinson's disease. In search for selective modulators of the D1 re...

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Detalhes bibliográficos
Autores:	García-Cárceles, Javier, Vázquez-Villa, Henar, Brea, José, Ladron de Guevara-Miranda, David, Cincilla, Giovanni, Sánchez-Martínez, Melchor, Sánchez-Merino, Anabel, Algar, Sergio, Teresa de Los Frailes, María, Roberts, Richard S, Ballesteros, Juan A, Rodríguez de Fonseca, Fernando, Benhamú, Bellinda, Loza, María I, López-Rodríguez, María L
Formato:	artículo
Fecha de publicación:	2022
País:	España
Recursos:	Instituto de Salud Carlos III (ISCIII)
Repositorio:	Repisalud
Idioma:	inglés
OAI Identifier:	oai:repisalud.isciii.es:20.500.12105/18754
Acesso em linha:	http://hdl.handle.net/20.500.12105/18754
Access Level:	acceso abierto
Palavra-chave:	Animals Biphenyl Compounds Cocaine Dopamine Dopamine Agents Dopamine Agonists Humans Indazoles Levodopa Ligands Mice Nitrofurans Parkinson Disease Receptors, Dopamine Receptors, Dopamine D1

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spelling	2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.García-Cárceles, JavierVázquez-Villa, HenarBrea, JoséLadron de Guevara-Miranda, DavidCincilla, GiovanniSánchez-Martínez, MelchorSánchez-Merino, AnabelAlgar, SergioTeresa de Los Frailes, MaríaRoberts, Richard SBallesteros, Juan ARodríguez de Fonseca, FernandoBenhamú, BellindaLoza, María ILópez-Rodríguez, María LAnimalsBiphenyl CompoundsCocaineDopamineDopamine AgentsDopamine AgonistsHumansIndazolesLevodopaLigandsMiceNitrofuransParkinson DiseaseReceptors, DopamineReceptors, Dopamine D1Tolerance development caused by dopamine replacement with l-DOPA and therapeutic drawbacks upon activation of dopaminergic receptors with orthosteric agonists reveal a significant unmet need for safe and effective treatment of Parkinson's disease. In search for selective modulators of the D1 receptor, the screening of a chemical library and subsequent medicinal chemistry program around an identified hit resulted in new synthetic compound 26 [UCM-1306, 2-(fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl] that increases the dopamine maximal effect in a dose-dependent manner in human and mouse D1 receptors, is inactive in the absence of dopamine, modulates dopamine affinity for the receptor, exhibits subtype selectivity, and displays low binding competition with orthosteric ligands. The new allosteric modulator potentiates cocaine-induced locomotion and enhances l-DOPA recovery of decreased locomotor activity in reserpinized mice after oral administration. The behavior of compound 26 supports the interest of a positive allosteric modulator of the D1 receptor as a promising therapeutic approach for Parkinson's disease.20242024-02-2720222022-08-3120222022-08-31research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.12105/18754reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/187542026-06-12T12:43:37Z
dc.title.none.fl_str_mv	2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.
title	2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.
spellingShingle	2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease. García-Cárceles, Javier Animals Biphenyl Compounds Cocaine Dopamine Dopamine Agents Dopamine Agonists Humans Indazoles Levodopa Ligands Mice Nitrofurans Parkinson Disease Receptors, Dopamine Receptors, Dopamine D1
title_short	2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.
title_full	2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.
title_fullStr	2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.
title_full_unstemmed	2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.
title_sort	2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.
dc.creator.none.fl_str_mv	García-Cárceles, Javier Vázquez-Villa, Henar Brea, José Ladron de Guevara-Miranda, David Cincilla, Giovanni Sánchez-Martínez, Melchor Sánchez-Merino, Anabel Algar, Sergio Teresa de Los Frailes, María Roberts, Richard S Ballesteros, Juan A Rodríguez de Fonseca, Fernando Benhamú, Bellinda Loza, María I López-Rodríguez, María L
author	García-Cárceles, Javier
author_facet	García-Cárceles, Javier Vázquez-Villa, Henar Brea, José Ladron de Guevara-Miranda, David Cincilla, Giovanni Sánchez-Martínez, Melchor Sánchez-Merino, Anabel Algar, Sergio Teresa de Los Frailes, María Roberts, Richard S Ballesteros, Juan A Rodríguez de Fonseca, Fernando Benhamú, Bellinda Loza, María I López-Rodríguez, María L
author_role	author
author2	Vázquez-Villa, Henar Brea, José Ladron de Guevara-Miranda, David Cincilla, Giovanni Sánchez-Martínez, Melchor Sánchez-Merino, Anabel Algar, Sergio Teresa de Los Frailes, María Roberts, Richard S Ballesteros, Juan A Rodríguez de Fonseca, Fernando Benhamú, Bellinda Loza, María I López-Rodríguez, María L
author2_role	author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv	Animals Biphenyl Compounds Cocaine Dopamine Dopamine Agents Dopamine Agonists Humans Indazoles Levodopa Ligands Mice Nitrofurans Parkinson Disease Receptors, Dopamine Receptors, Dopamine D1
topic	Animals Biphenyl Compounds Cocaine Dopamine Dopamine Agents Dopamine Agonists Humans Indazoles Levodopa Ligands Mice Nitrofurans Parkinson Disease Receptors, Dopamine Receptors, Dopamine D1
description	Tolerance development caused by dopamine replacement with l-DOPA and therapeutic drawbacks upon activation of dopaminergic receptors with orthosteric agonists reveal a significant unmet need for safe and effective treatment of Parkinson's disease. In search for selective modulators of the D1 receptor, the screening of a chemical library and subsequent medicinal chemistry program around an identified hit resulted in new synthetic compound 26 [UCM-1306, 2-(fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl] that increases the dopamine maximal effect in a dose-dependent manner in human and mouse D1 receptors, is inactive in the absence of dopamine, modulates dopamine affinity for the receptor, exhibits subtype selectivity, and displays low binding competition with orthosteric ligands. The new allosteric modulator potentiates cocaine-induced locomotion and enhances l-DOPA recovery of decreased locomotor activity in reserpinized mice after oral administration. The behavior of compound 26 supports the interest of a positive allosteric modulator of the D1 receptor as a promising therapeutic approach for Parkinson's disease.
publishDate	2022
dc.date.none.fl_str_mv	2022 2022-08-31 2022 2022-08-31 2024 2024-02-27
dc.type.none.fl_str_mv	research article http://purl.org/coar/resource_type/c_2df8fbb1 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	http://hdl.handle.net/20.500.12105/18754
url	http://hdl.handle.net/20.500.12105/18754
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/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 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.source.none.fl_str_mv	reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII)
instname_str	Instituto de Salud Carlos III (ISCIII)
reponame_str	Repisalud
collection	Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_	1869406381210075136
score	15,198674

2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.

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