Functionally selective and biased agonists of muscarinic receptors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F21%3A00542922" target="_blank" >RIV/67985823:_____/21:00542922 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/j.phrs.2021.105641" target="_blank" >https://doi.org/10.1016/j.phrs.2021.105641</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.phrs.2021.105641" target="_blank" >10.1016/j.phrs.2021.105641</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Functionally selective and biased agonists of muscarinic receptors

Popis výsledku v původním jazyce

Disruption of cholinergic signalling via muscarinic receptors is associated with various pathologies, like Alzheimer’s disease or schizophrenia. Selective muscarinic agonists possess therapeutic potential in the treatment of diabetes, pain or Sjögren's syndrome. The orthosteric binding site of all subtypes of the muscarinic receptor is structurally identical, making the development of affinity-based selective agonists virtually impossible. Some agonists, however, are functionally selective, they activate only a subset of receptors or signalling pathways. Others may stabilise specific conformations of the receptor leading to non-uniform modulation of individual signalling pathways (biased agonists). Functionally selective and biased agonists represent a promising approach for selective activation of individual subtypes of muscarinic receptors. In this work we review chemical structures, receptor binding and agonist-specific conformations of currently known functionally selective and biased muscarinic agonists in the context of their intricate intracellular signalling. Further, we take a perspective on the possible use of biased agonists for tissue and organ-specific activation of muscarinic receptors.

Název v anglickém jazyce

Functionally selective and biased agonists of muscarinic receptors

Popis výsledku anglicky

Disruption of cholinergic signalling via muscarinic receptors is associated with various pathologies, like Alzheimer’s disease or schizophrenia. Selective muscarinic agonists possess therapeutic potential in the treatment of diabetes, pain or Sjögren's syndrome. The orthosteric binding site of all subtypes of the muscarinic receptor is structurally identical, making the development of affinity-based selective agonists virtually impossible. Some agonists, however, are functionally selective, they activate only a subset of receptors or signalling pathways. Others may stabilise specific conformations of the receptor leading to non-uniform modulation of individual signalling pathways (biased agonists). Functionally selective and biased agonists represent a promising approach for selective activation of individual subtypes of muscarinic receptors. In this work we review chemical structures, receptor binding and agonist-specific conformations of currently known functionally selective and biased muscarinic agonists in the context of their intricate intracellular signalling. Further, we take a perspective on the possible use of biased agonists for tissue and organ-specific activation of muscarinic receptors.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/GJ19-06106Y" target="_blank" >GJ19-06106Y: Analýza signalizačního biasu nově syntetizovaných muskarinových agonistů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Pharmacological Research

ISSN

1043-6618

e-ISSN

1096-1186

Svazek periodika

169

Číslo periodika v rámci svazku

July

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

105641

Kód UT WoS článku

000663005100028

EID výsledku v databázi Scopus

2-s2.0-85105477143