G protein-coupled receptors: structure-and function-based drug discovery

D Yang, Q Zhou, V Labroska, S Qin… - Signal transduction and …, 2021‏ - nature.com
As one of the most successful therapeutic target families, G protein-coupled receptors
(GPCRs) have experienced a transformation from random ligand screening to knowledge …

The interplay of glucagon-like peptide-1 receptor trafficking and signalling in pancreatic beta cells

A Marzook, A Tomas, B Jones - Frontiers in endocrinology, 2021‏ - frontiersin.org
The glucagon-like peptide 1 receptor (GLP-1R) is a class BG protein-coupled receptor
(GPCR) which mediates the effects of GLP-1, an incretin hormone secreted primarily from L …

Positive allosteric modulation of a GPCR ternary complex

WAC Burger, CJ Draper-Joyce, C Valant… - Science …, 2024‏ - science.org
The activation of a G protein–coupled receptor (GPCR) leads to the formation of a ternary
complex between agonist, receptor, and G protein that is characterized by high-affinity …

Pharmacological selection of cannabinoid receptor effectors: Signalling, allosteric modulation and bias

JJ Manning, HM Green, M Glass, DB Finlay - Neuropharmacology, 2021‏ - Elsevier
The type-1 cannabinoid receptor (CB 1) is a promising drug target for a wide range of
diseases. However, many existing and novel candidate ligands for CB 1 have shown only …

Analyzing kinetic signaling data for G-protein-coupled receptors

SRJ Hoare, PH Tewson, AM Quinn, TE Hughes… - Scientific reports, 2020‏ - nature.com
In classical pharmacology, bioassay data are fit to general equations (eg the dose response
equation) to determine empirical drug parameters (eg EC50 and Emax), which are then …

Molecular Spies in Action: Genetically Encoded Fluorescent Biosensors Light up Cellular Signals

AMM Gest, AZ Sahan, Y Zhong, W Lin, S Mehta… - Chemical …, 2024‏ - ACS Publications
Cellular function is controlled through intricate networks of signals, which lead to the myriad
pathways governing cell fate. Fluorescent biosensors have enabled the study of these …

Bias translation: The final frontier?

T Kenakin - British Journal of Pharmacology, 2024‏ - Wiley Online Library
Biased signalling is a natural result of GPCR allosteric function and should be expected from
any and all synthetic and natural agonists. Therefore, it may be encountered in all agonist …

Genetically encoded fluorescent biosensors for GPCR research

H Kim, IY Baek, J Seong - Frontiers in Cell and Developmental …, 2022‏ - frontiersin.org
G protein-coupled receptors (GPCRs) regulate a wide range of physiological and
pathophysiological cellular processes, thus it is important to understand how GPCRs are …

Quantifying the kinetics of signaling and arrestin recruitment by nervous system G-protein coupled receptors

SRJ Hoare, PH Tewson, S Sachdev… - Frontiers in Cellular …, 2022‏ - frontiersin.org
Neurons integrate inputs over different time and space scales. Fast excitatory synapses at
boutons (ms and μm), and slow modulation over entire dendritic arbors (seconds and mm) …

[HTML][HTML] Partial agonism improves the anti-hyperglycaemic efficacy of an oxyntomodulin-derived GLP-1R/GCGR co-agonist

P Pickford, M Lucey, RM Rujan, ER McGlone, S Bitsi… - Molecular …, 2021‏ - Elsevier
Objective Glucagon-like peptide-1 and glucagon receptor (GLP-1R/GCGR) co-agonism can
maximise weight loss and improve glycaemic control in type 2 diabetes and obesity. In this …