Chemoproteomic Approach to Explore the Target Profile of GPCR ligands: Application to 5-HT1A and 5-HT6 Receptors.
Chemistry
; 22(4): 1313-21, 2016 Jan 22.
Article
em En
| MEDLINE
| ID: mdl-26560738
ABSTRACT
Determination of the targets of a compound remains an essential aspect in drug discovery. A complete understanding of all binding interactions is critical to recognize in advance both therapeutic effects and undesired consequences. However, the complete polypharmacology of many drugs currently in clinical development is still unknown, especially in the case of Gâ
protein-coupled receptor (GPCR) ligands. In this work we have developed a chemoproteomic platform based on the use of chemical probes to explore the target profile of a compound in biological systems. As proof of concept, this methodology has been applied to selected ligands of the therapeutically relevant serotonin 5-HT1A and 5-HT6 receptors, and we have identified and validated some of their off-targets. This approach could be extended to other drugs of interest to study the targeted proteome in disease-relevant systems.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Serotonina
/
Receptores Acoplados a Proteínas G
/
Receptor 5-HT1A de Serotonina
Limite:
Humans
Idioma:
En
Revista:
Chemistry
Assunto da revista:
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Espanha