Homodimerization of Cb2 Cannabinoid Receptor Triggered by a Bivalent Ligand Enhances Cellular Signaling DOI
Gemma Navarro, Marc Gómez‐Autet, Paula Morales

и другие.

Опубликована: Янв. 1, 2024

G protein-coupled receptors (GPCRs) exist within a landscape of interconvertible conformational states and in dynamic equilibrium between monomers higher-order oligomers, both influenced by ligand binding. Here, we have shown that homobivalent formed equal chromenopyrazole moieties as pharmacophores, connected 14 methylene units, can modulate the dynamics cannabinoid CB2 receptor (CB2R) homodimerization simultaneously binding protomers CB2R-CB2R homodimer. Computational pharmacological experimentals showed one pharmacophores binds to orthosteric site protomer, other pharmacophore membrane-oriented pocket transmembranes 1 7 partner protomer. This provides unique properties, such increased potency Gi recruitment β-arrestin. Thus, modulating dimerization dynamics, it may be possible fine-tune CB2R activity with potentially improved therapeutic outcomes.

Язык: Английский

Homodimerization of CB2 cannabinoid receptor triggered by a bivalent ligand enhances cellular signaling DOI Creative Commons
Gemma Navarro, Marc Gómez‐Autet, Paula Morales

и другие.

Pharmacological Research, Год журнала: 2024, Номер 208, С. 107363 - 107363

Опубликована: Авг. 23, 2024

G protein-coupled receptors (GPCRs) exist within a landscape of interconvertible conformational states and in dynamic equilibrium between monomers higher-order oligomers, both influenced by ligand binding. Here, we show that homobivalent formed equal chromenopyrazole moieties as pharmacophores, connected 14 methylene units, can modulate the dynamics cannabinoid CB

Язык: Английский

Процитировано

19
Evolution and challenges of opioids in pain management: Understanding mechanisms and exploring strategies for safer analgesics DOI

Toluwalope Temitope Bakare,

Henrietta Onyinye Uzoeto,

Laywonmen Newon Gonlepa

и другие.

Medicinal Chemistry Research, Год журнала: 2024, Номер 33(4), С. 563 - 579

Опубликована: Фев. 29, 2024

Язык: Английский

Процитировано

3
Allosteric Modulators of Serotonin Receptors: A Medicinal Chemistry Survey DOI Creative Commons
Leonardo Brunetti, Fabio Francavilla, Marcello Leopoldo

и другие.

Pharmaceuticals, Год журнала: 2024, Номер 17(6), С. 695 - 695

Опубликована: Май 28, 2024

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter regulating numerous physiological functions, and its dysregulation crucial component of the pathological processes schizophrenia, depression, migraines, obesity. 5-HT interacts with 14 different receptors, which 5-HT1A-1FRs, 5-HT2A-CRs, 5-HT4-7Rs are G protein-coupled receptors (GPCRs), while 5-HT3R ligand-gated ion channel. Over years, selective orthosteric ligands have been identified for almost all serotonin yielding several clinically relevant drugs. However, high degree homology between 5-HTRs other GPCRs means that can severe side effects. Thus, there has recently increased interest in developing safer GPCRs, bind to less conserved, more specific sites, distinct from receptor’s natural ligand. The present review describes identification allosteric largely compounds (oleamide, cannabidiol, THC, aporphine alkaloids), complemented by synthetic modulators developed large part 5-HT2C receptor. latter positive sought after their potential as drugs preferable over agonists antiobesity agents potentially profile. When available, details on interactions ligand binding site will be provided. An outlook future research field also

Язык: Английский

Процитировано

3
Design, synthesis and biological evaluation of dual inhibitors targeting AR/AR-Vs and PARP1 in castration resistant prostate cancer therapy DOI Open Access

Si-Han Zhang,

Yaowu Su,

Mengzhu Zheng

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 180, С. 117485 - 117485

Опубликована: Сен. 25, 2024

Язык: Английский

Процитировано

3
Chemical probe as specific detector of porcine protein or peptide in meat and meat-based products: Potential applications, challenges, and the way forward DOI Creative Commons
Mohd Nurhadi Hamsar, Awis Qurni Sazili, Siti Farah Md Tohid

и другие.

Journal of Agriculture and Food Research, Год журнала: 2024, Номер 15, С. 101026 - 101026

Опубликована: Янв. 29, 2024

This review discusses the potential use of chemical probes for detecting porcine protein/peptide in meat and meat-based products. Porcine detection is important religious, cultural, food safety reasons. Chemical probe has emerged as a tool sensitive specific various proteins. provides an overview different types probes, their advantages, limitations. The current applications industry are also discussed, along with challenges that must be addressed effective use. article concludes by emphasizing importance valuable need further research development to advance

Язык: Английский

Процитировано

2
Active Discovery of the Allosteric Inhibitor Targeting Botrytis cinerea Chitinase Based on Neural Relational Inference for Food Preservation DOI
Hongsu Wang, Chenyang Wang, Ziyou Wang

и другие.

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(29), С. 16128 - 16139

Опубликована: Июль 9, 2024

Currently, allosteric inhibitors have emerged as an effective strategy in the development of preservatives against drug-resistant

Язык: Английский

Процитировано

2
Designed dualsteric modulators: A novel route for drug discovery DOI

Nuan Li,

Guodong Zheng, Lili Fu

и другие.

Drug Discovery Today, Год журнала: 2024, Номер 29(10), С. 104141 - 104141

Опубликована: Авг. 19, 2024

Язык: Английский

Процитировано

1
Homodimerization of CB2cannabinoid receptor triggered by a bivalent ligand enhances cellular signaling DOI Open Access
Gemma Navarro, Marc Gómez‐Autet, Paula Morales

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 11, 2024

ABSTRACT G protein-coupled receptors (GPCRs) exist within a landscape of interconvertible conformational states and in dynamic equilibrium between monomers higher-order oligomers, both influenced by ligand binding. Here, we have shown that homobivalent formed equal chromenopyrazole moieties as pharmacophores, connected 14 methylene units, can modulate the dynamics cannabinoid CB 2 receptor (CB R) homodimerization simultaneously binding protomers R-CB R homodimer. Computational pharmacological experimentals showed one pharmacophores binds to orthosteric site protomer, other pharmacophore membrane-oriented pocket transmembranes 1 7 partner protomer. This provides unique properties, such increased potency i recruitment β-arrestin. Thus, modulating dimerization dynamics, it may be possible fine-tune activity with potentially improved therapeutic outcomes. HIGHLIGHTS A (PM369) modulates PM369 protomer complementary, membrane-facing, triggers via TM 1/7 interface properties potentiates signaling, β-arrestin These results highlight new approaches control GPCR signaling GRAPHICAL

Язык: Английский

Процитировано

0
Homodimerization of Cb2 Cannabinoid Receptor Triggered by a Bivalent Ligand Enhances Cellular Signaling DOI
Gemma Navarro, Marc Gómez‐Autet, Paula Morales

и другие.

Опубликована: Янв. 1, 2024

G protein-coupled receptors (GPCRs) exist within a landscape of interconvertible conformational states and in dynamic equilibrium between monomers higher-order oligomers, both influenced by ligand binding. Here, we have shown that homobivalent formed equal chromenopyrazole moieties as pharmacophores, connected 14 methylene units, can modulate the dynamics cannabinoid CB2 receptor (CB2R) homodimerization simultaneously binding protomers CB2R-CB2R homodimer. Computational pharmacological experimentals showed one pharmacophores binds to orthosteric site protomer, other pharmacophore membrane-oriented pocket transmembranes 1 7 partner protomer. This provides unique properties, such increased potency Gi recruitment β-arrestin. Thus, modulating dimerization dynamics, it may be possible fine-tune CB2R activity with potentially improved therapeutic outcomes.

Язык: Английский

Процитировано

0