Discovery of Guanfacine as a Novel TAAR1 Agonist: A Combination Strategy through Molecular Modeling Studies and Biological Assays.

AlphaFold GPCR QSAR TAAR1 docking dopamine guanfacine α2-adrenoreceptor

Journal

Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453

Informations de publication

Date de publication:
20 Nov 2023
Historique:
received: 16 10 2023
revised: 09 11 2023
accepted: 17 11 2023
medline: 25 11 2023
pubmed: 25 11 2023
entrez: 25 11 2023
Statut: epublish

Résumé

Trace amine-associated receptor 1 (TAAR1) is an attractive target for the design of innovative drugs to be applied in diverse pharmacological settings. Due to a non-negligible structural similarity with endogenous ligands, most of the agonists developed so far resulted in being affected by a low selectivity for TAAR1 with respect to other monoaminergic G protein-coupled receptors, like the adrenoreceptors. This study utilized comparative molecular docking studies and quantitative-structure activity relationship (QSAR) analyses to unveil key structural differences between TAAR1 and alpha2-adrenoreceptor (α

Identifiants

pubmed: 38004497
pii: ph16111632
doi: 10.3390/ph16111632
pmc: PMC10674299
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : NIGMS NIH HHS
ID : P41 GM103311
Pays : United States

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Auteurs

Elena Cichero (E)

Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, 16132 Genoa, Italy.

Valeria Francesconi (V)

Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, 16132 Genoa, Italy.

Beatrice Casini (B)

Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, 16132 Genoa, Italy.

Monica Casale (M)

Section of Chemistry and Food and Pharmaceutical Technologies, University of Genoa, 16148 Genoa, Italy.

Evgeny Kanov (E)

Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia.
St. Petersburg University Hospital, St. Petersburg State University, 199034 St. Petersburg, Russia.

Andrey S Gerasimov (AS)

Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia.

Ilya Sukhanov (I)

Valdman Institute of Pharmacology, Pavlov First St. Petersburg State Medical University, 197022 St. Petersburg, Russia.

Artem Savchenko (A)

Valdman Institute of Pharmacology, Pavlov First St. Petersburg State Medical University, 197022 St. Petersburg, Russia.

Stefano Espinoza (S)

Department of Health Sciences and Research Center on Autoimmune and Allergic Diseases (CAAD), University of Piemonte Orientale (UPO), 28100 Novara, Italy.
Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT), 16152 Genova, Italy.

Raul R Gainetdinov (RR)

Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia.
St. Petersburg University Hospital, St. Petersburg State University, 199034 St. Petersburg, Russia.

Michele Tonelli (M)

Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, 16132 Genoa, Italy.

Classifications MeSH