Biased Signaling in G Protein-Coupled Receptors: Understanding the Biological Relevance and Tools for Probing Functionally Selective Ligands DOI
Braden S. Fallon,

Kathleen E. Rondem,

Elizabeth J. Mumby

et al.

Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Biased signaling has transformed pharmacology by revealing that receptors, particularly G protein-coupled receptors (GPCRs), can activate specific intracellular pathways selectively rather than uniformly. This discovery enables the development of targeted therapeutics minimize side effects precisely modulating receptor activity. Functionally selective ligands, which preferentially distinct branches, have become essential tools for exploring mechanisms and uncovering complexities GPCR signaling. These ligands help clarify function in various physiological pathological contexts, offering profound implications therapeutic innovation. GPCRs, mediate a wide range cellular responses through coupling to proteins arrestins, are key pharmacological targets, with nearly third FDA-approved drugs acting on them. Recent advancements biosensor development, multiplex assay platforms, deep mutational scanning methods improving our ability define signaling, allowing better understanding biased pathways.

Language: Английский

Molecular basis of proton sensing by G protein-coupled receptors DOI
Matthew K. Howard, Nick Hoppe, Xi‐Ping Huang

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

7
Biased Signaling in G Protein-Coupled Receptors: Understanding the Biological Relevance and Tools for Probing Functionally Selective Ligands DOI
Braden S. Fallon,

Kathleen E. Rondem,

Elizabeth J. Mumby

et al.

Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Biased signaling has transformed pharmacology by revealing that receptors, particularly G protein-coupled receptors (GPCRs), can activate specific intracellular pathways selectively rather than uniformly. This discovery enables the development of targeted therapeutics minimize side effects precisely modulating receptor activity. Functionally selective ligands, which preferentially distinct branches, have become essential tools for exploring mechanisms and uncovering complexities GPCR signaling. These ligands help clarify function in various physiological pathological contexts, offering profound implications therapeutic innovation. GPCRs, mediate a wide range cellular responses through coupling to proteins arrestins, are key pharmacological targets, with nearly third FDA-approved drugs acting on them. Recent advancements biosensor development, multiplex assay platforms, deep mutational scanning methods improving our ability define signaling, allowing better understanding biased pathways.

Language: Английский

Citations

0