Identification of a Cannabinoid Receptor 2 Allosteric Site Using Computational Modeling and Pharmacological Analysis

ACS Pharmacology & Translational Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Emerging evidence has demonstrated that cannabinoid receptor 2 (CB2) is involved in a number of diseases, such as neurodegenerative disorders and various types cancer, making it an attractive pharmacological target. Classically, protein active site or orthosteric binding site, where the endogenous ligand binds to, used target for design most small-molecule drugs. This can present challenges when comes to phylogenetically related proteins have similar sites, receptors. An alternative approach sites are unique these receptors yet still impact function, known allosteric sites. Using inactive-state human crystal structure (PDB ID:5ZTY), we identified putative CB2 using computational approaches. In vitro signaling assays modulators agonists been verify silico results. identification opens promising avenues development selective specific ligands therapeutic purposes.

Язык: Английский

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Advances in cannabinoid receptors pharmacology: from receptor structural insights to ligand discovery

Acta Pharmacologica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Язык: Английский

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GPCR-Mediated Natural Products and Compounds: Potential Therapeutic Targets for the Treatment of Neurological Diseases

Pharmacological Research, Год журнала: 2024, Номер 208, С. 107395 - 107395

Опубликована: Сен. 4, 2024

Язык: Английский

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Differential Behavior of Conformational Dynamics in Active and Inactive States of Cannabinoid Receptor 1

The Journal of Physical Chemistry B, Год журнала: 2024, Номер 128(35), С. 8437 - 8447

Опубликована: Авг. 22, 2024

Cannabinoid receptor 1 (CB1) is a G protein-coupled that regulates critical physiological processes including pain, appetite, and cognition. Understanding the conformational dynamics of CB1 associated with transitions between inactive active signaling states imperative for developing targeted modulators. Using microsecond-level all-atom molecular simulations, we identified marked differences in ensembles

Язык: Английский

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Could positive allosteric modulators of the cannabinoid CB1 receptor be efficacious and safe for the treatment of chronic pain?

Current Opinion in Pharmacology, Год журнала: 2024, Номер 79, С. 102495 - 102495

Опубликована: Окт. 23, 2024

Язык: Английский

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