Pharmacologically targeting intracellular allosteric sites of GPCRs for drug discovery.
G-protein-coupled receptors (GPCRs)
allosteric modulators
allostery
biased signaling
intracellular allosteric site
Journal
Drug discovery today
ISSN: 1878-5832
Titre abrégé: Drug Discov Today
Pays: England
ID NLM: 9604391
Informations de publication
Date de publication:
17 Oct 2023
17 Oct 2023
Historique:
received:
12
09
2023
revised:
07
10
2023
accepted:
12
10
2023
pubmed:
19
10
2023
medline:
19
10
2023
entrez:
18
10
2023
Statut:
aheadofprint
Résumé
G-protein-coupled receptors (GPCRs) are a family of cell surface proteins that can sense a variety of extracellular stimuli and mediate multiple signaling transduction pathways involved in human physiology. Recent advances in GPCR structural biology have revealed a relatively conserved intracellular allosteric site in multiple GPCRs, which can be utilized to modulate receptors from the inside. This novel intracellular site partially overlaps with the G-protein and β-arrestin coupling sites, providing a novel avenue for biological intervention. Here, we review evidence available for GPCR structures complexed with intracellular small-molecule allosteric modulators, elucidating drug-target interactions and allosteric mechanisms. Moreover, we highlight the potential of intracellular allosteric modulators in achieving biased signaling, which provides insights into biased allosteric mechanisms.
Identifiants
pubmed: 37852356
pii: S1359-6446(23)00319-7
doi: 10.1016/j.drudis.2023.103803
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
103803Informations de copyright
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