Design of Negative and Positive Allosteric Modulators of the Cannabinoid CB2Receptor Derived from the Natural Product Cannabidiol

Gemma Navarro; Angel Gonzalez; Adrià Sánchez-Morales; Nil Casajuana-Martin; Marc Gómez-Ventura; Arnau Cordomí; Félix Busqué; Ramon Alibés; Leonardo Pardo; Rafael Franco

doi:10.1021/acs.jmedchem.1c00561

Design of Negative and Positive Allosteric Modulators of the Cannabinoid CB₂Receptor Derived from the Natural Product Cannabidiol

Gemma Navarro, Angel Gonzalez, Adrià Sánchez-Morales, Nil Casajuana-Martin, Marc Gómez-Ventura, Arnau Cordomí, Félix Busqué, Ramon Alibés, Leonardo Pardo, Rafael Franco^*

^*Autor correspondiente de este trabajo

Producción científica: Contribución a una revista › Artículo › Investigación › revisión exhaustiva

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Resumen

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.

Idioma original	Inglés
Páginas (desde-hasta)	9354-9364
Número de páginas	11
Publicación	Journal of Medicinal Chemistry
Volumen	64
N.º	13
DOI	https://doi.org/10.1021/acs.jmedchem.1c00561
Estado	Publicada - 8 jul 2021

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10.1021/acs.jmedchem.1c00561

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Navarro, G., Gonzalez, A., Sánchez-Morales, A., Casajuana-Martin, N., Gómez-Ventura, M., Cordomí, A., Busqué, F., Alibés, R., Pardo, L., & Franco, R. (2021). Design of Negative and Positive Allosteric Modulators of the Cannabinoid CB₂Receptor Derived from the Natural Product Cannabidiol. Journal of Medicinal Chemistry, 64(13), 9354-9364. https://doi.org/10.1021/acs.jmedchem.1c00561

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title = "Design of Negative and Positive Allosteric Modulators of the Cannabinoid CB2Receptor Derived from the Natural Product Cannabidiol",

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.",

author = "Gemma Navarro and Angel Gonzalez and Adri{\`a} S{\'a}nchez-Morales and Nil Casajuana-Martin and Marc G{\'o}mez-Ventura and Arnau Cordom{\'i} and F{\'e}lix Busqu{\'e} and Ramon Alib{\'e}s and Leonardo Pardo and Rafael Franco",

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year = "2021",

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Navarro, G, Gonzalez, A, Sánchez-Morales, A, Casajuana-Martin, N, Gómez-Ventura, M, Cordomí, A , Busqué, F , Alibés, R , Pardo, L & Franco, R 2021, 'Design of Negative and Positive Allosteric Modulators of the Cannabinoid CB₂Receptor Derived from the Natural Product Cannabidiol', Journal of Medicinal Chemistry, vol. 64, n.º 13, pp. 9354-9364. https://doi.org/10.1021/acs.jmedchem.1c00561

Design of Negative and Positive Allosteric Modulators of the Cannabinoid CB₂Receptor Derived from the Natural Product Cannabidiol. / Navarro, Gemma; Gonzalez, Angel; Sánchez-Morales, Adrià et al.
En: Journal of Medicinal Chemistry, Vol. 64, N.º 13, 08.07.2021, p. 9354-9364.

Producción científica: Contribución a una revista › Artículo › Investigación › revisión exhaustiva

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AU - Navarro, Gemma

AU - Gonzalez, Angel

AU - Sánchez-Morales, Adrià

AU - Casajuana-Martin, Nil

AU - Gómez-Ventura, Marc

AU - Cordomí, Arnau

AU - Busqué, Félix

AU - Alibés, Ramon

AU - Pardo, Leonardo

AU - Franco, Rafael

PY - 2021/7/8

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