Targeting receptor complexes: a new dimension in drug discovery
Research output: Contribution to journal › Review › Research › peer-review
Targeting receptor proteins, such as ligand-gated ion channels and G protein-coupled receptors, has directly enabled the discovery of most drugs developed to modulate receptor signalling. However, as the search for novel and improved drugs continues, an innovative approach - targeting receptor complexes - is emerging. Receptor complexes are composed of core receptor proteins and receptor-associated proteins, which have profound effects on the overall receptor structure, function and localization. Hence, targeting key protein-protein interactions within receptor complexes provides an opportunity to develop more selective drugs with fewer side effects. In this Review, we discuss our current understanding of ligand-gated ion channel and G protein-coupled receptor complexes and discuss strategies for their pharmacological modulation. Although such strategies are still in preclinical development for most receptor complexes, they exemplify how receptor complexes can be drugged, and lay the groundwork for this nascent area of research.
Targeting protein complexes, including those containing G protein-coupled receptors or ligand-gated ion channels, could provide opportunities to increase the target and functional selectivity of novel drugs compared with existing therapies, which only target the receptors. This Review discusses the landscape of ligand-gated ion channel and G protein-coupled receptor complexes as therapeutic targets, as well as strategies for their pharmacological modulation.
Original language | English |
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Journal | Nature Reviews. Drug Discovery |
Volume | 19 |
Pages (from-to) | 884-901 |
Number of pages | 18 |
ISSN | 1474-1776 |
DOIs | |
Publication status | Published - 2020 |
- GENE-RELATED PEPTIDE, PROTEIN-PROTEIN INTERACTIONS, SMALL-MOLECULE INHIBITORS, NATIVE GABA(B) RECEPTORS, NEURONAL NITRIC-OXIDE, PICK1 PDZ DOMAIN, AMPA RECEPTORS, DOUBLE-BLIND, AUXILIARY SUBUNITS, SULFONYLUREA RECEPTOR
Research areas
ID: 252306684