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- W4387662565 abstract "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. Teaser: We review the high-resolution structural advances and allosteric pharmacology of small-molecule modulators targeting the GPCR intracellular signaling protein interface." @default.
- W4387662565 created "2023-10-17" @default.
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- W4387662565 date "2023-10-01" @default.
- W4387662565 modified "2023-10-17" @default.
- W4387662565 title "Pharmacologically targeting intracellular allosteric sites of GPCRs for drug discovery" @default.
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- W4387662565 doi "https://doi.org/10.1016/j.drudis.2023.103803" @default.
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