Design of Negative and Positive Allosteric Modulators of the Cannabinoid CB2 Receptor Derived from the Natural Product Cannabidiol.
J Med Chem
; 64(13): 9354-9364, 2021 07 08.
Article
en En
| MEDLINE
| ID: mdl-34161090
ABSTRACT
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Productos Biológicos
/
Cannabidiol
/
Diseño de Fármacos
/
Receptor Cannabinoide CB2
/
Agonistas de Receptores de Cannabinoides
Límite:
Humans
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
España