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 corresponent d’aquest treball

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30 Cites (Scopus)

1 Descàrregues (Pure)

Resum

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	Anglès
Pàgines (de-a)	9354-9364
Nombre de pàgines	11
Revista	Journal of Medicinal Chemistry
Volum	64
Número	13
DOIs	https://doi.org/10.1021/acs.jmedchem.1c00561
Estat de la publicació	Publicada - 8 de jul. 2021

Accés al document

10.1021/acs.jmedchem.1c00561

https://ddd.uab.cat/record/279275

Altres arxius i enllaços

Link to publication in Scopus

Com citar-ho

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

@article{cfd181d91360436f96344fda75ad8c3b,

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",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors. Published by American Chemical Society.",

year = "2021",

month = jul,

day = "8",

doi = "10.1021/acs.jmedchem.1c00561",

language = "English",

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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, núm. 13, pàg. 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.
In: Journal of Medicinal Chemistry, Vol. 64, Núm. 13, 08.07.2021, pàg. 9354-9364.

Producció científica: Contribució a revista › Article › Recerca › Avaluat per experts

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T1 - Design of Negative and Positive Allosteric Modulators of the Cannabinoid CB2Receptor Derived from the Natural Product Cannabidiol

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

Y1 - 2021/7/8

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AB - 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.

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