Results 1 to 10 of about 11,641 (225)

A structural mechanism of nuclear receptor biased agonism [PDF]

Proceedings of the National Academy of Sciences of the United States of America, 2022
Efforts to decrease the adverse effects of nuclear receptor (NR) drugs have yielded experimental agonists that produce better outcomes in mice. Some of these agonists have been shown to cause different, not just less intense, on-target transcriptomic effects; however, a structural explanation for such agonist-specific effects remains unknown.
Michelle D Nemetchek, Travis S Hughes, Mariah L Rayl   +2 more
exaly   +4 more sources

Ligand recognition and biased agonism of the D1 dopamine receptor [PDF]

Nature Communications, 2022
D1 dopamine receptor is an important drug target for treatment of hypertension and Parkinson’s disease. Here, authors report three cryo-EM structures of the D1R-Gs complex bound to three distinct D1R-selective drugs.
Xiao Teng, Sijia Chen, Yingying Nie, Peng Xiao, Xiao Yu, Zhenhua Shao, Sanduo Zheng   +6 more
doaj   +4 more sources

The role of kinetic context in apparent biased agonism at GPCRs [PDF]

Nature Communications, 2016
Biased agonists act at a receptor to preferentially induce distinct intracellular signalling responses over others. Here the authors show how kinetics of ligand binding and signaling responses greatly influence observed bias profiles, and hence must be ...
Carmen Klein Herenbrink, David A. Sykes, Prashant Donthamsetti, Meritxell Canals, Thomas Coudrat, Jeremy Shonberg, Peter J. Scammells, Ben Capuano, Patrick M. Sexton, Steven J. Charlton, Jonathan A. Javitch, Arthur Christopoulos, J. Robert Lane   +12 more
doaj   +5 more sources

Biased agonism: the quest for the analgesic holy grail [PDF]

PAIN Reports, 2018
. Opioids alleviate pain, but adverse effects severely limit their usefulness. To solve this problem, biased ligands favoring 1 signaling pathway downstream of the μ-opioid receptor over another are being developed.
M. Alexander Stanczyk, Ram Kandasamy
doaj   +4 more sources

Exploring Biased Agonism at FPR1 as a Means to Encode Danger Sensing [PDF]

Cells, 2020
Ligand-based selectivity in signal transduction (biased signaling) is an emerging field of G protein-coupled receptor (GPCR) research and might allow the development of drugs with targeted activation profiles.
Jieny Gröper, Gabriele M. König, Evi Kostenis, Volker Gerke, Carsten A. Raabe, Ursula Rescher   +5 more
doaj   +5 more sources

Biased agonism at chemokine receptors. [PDF]

Cell Signal, 2021
In the human chemokine system, interactions between the approximately 50 known endogenous chemokine ligands and 20 known chemokine receptors (CKRs) regulate a wide range of cellular functions and biological processes including immune cell activation and homeostasis, development, angiogenesis, and neuromodulation.
Eiger DS, Boldizsar N, Honeycutt CC, Gardner J, Rajagopal S.   +4 more
europepmc   +4 more sources

Modelling G protein-biased agonism using GLP-1 receptor C-terminal mutations [PDF]

Molecular Metabolism
Background and aim: The glucagon-like peptide-1 receptor (GLP-1R) is a major therapeutic target for type 2 diabetes and obesity. Agonists showing bias in favour of G protein signalling over β-arrestin recruitment and GLP-1R internalisation, e.g ...
Hanh Duyen Tran, Yiming Zuo, Carissa Wong, Alice Pollard, Steve Bloom, Ben Jones   +5 more
doaj   +2 more sources

Biased agonism of GLP-1R and GIPR enhances glucose lowering and weight loss, with dual GLP-1R/GIPR biased agonism yielding greater efficacy [PDF]

Cell Reports Medicine
Summary: Glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists have recently been shown to play a significant role in the treatment of diabetes and obesity.
Ruben Rodriguez, Anne Hergarden, Shyam Krishnan, Marikris Morales, Davina Lam, Ted Tracy, Teresa Tang, Avalon Patton, Craig Lee, Asmita Pant, Daniel A. Erlanson, Johan Enquist, Derek Bone, Ray Fucini, Damian Bialonczyk, Stig K. Hansen, Jian Luo, Manu V. Chakravarthy   +17 more
doaj   +2 more sources

The β-blocker Nebivolol Is a GRK/β-arrestin biased agonist. [PDF]

PLoS ONE, 2013
Nebivolol, a third generation β-adrenoceptor (β-AR) antagonist (β-blocker), causes vasodilation by inducing nitric oxide (NO) production. The mechanism via which nebivolol induces NO production remains unknown, resulting in the genesis of much of the ...
Catherine E Erickson, Rukhsana Gul, Christopher P Blessing, Jenny Nguyen, Tammy Liu, Lakshmi Pulakat, Murat Bastepe, Edwin K Jackson, Bradley T Andresen   +8 more
doaj   +9 more sources

Biased agonism at β-adrenergic receptors. [PDF]

Cell Signal, 2021
The β-adrenergic receptors (βARs) include three subtypes, β1, β2 and β3. These receptors are widely expressed and regulate numerous physiological processes including cardiovascular and metabolic functions and airway tone. The βARs are also important targets in the treatment of many diseases including hypertension, heart failure and asthma.
Ippolito M, Benovic JL.
europepmc   +3 more sources