The role of kinetic context in apparent biased agonism at GPCRs [PDF]
Nature Communications, 2016 Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually
A Akinc +62 more
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Hyperactivity in Mice Induced by Opioid Agonists with Partial Intrinsic Efficacy and Biased Agonism Administered Alone and in Combination with Morphine. [PDF]
Biomolecules, 2023 Opioid analgesics such as morphine and fentanyl induce mu-opioid receptor (MOR)-mediated hyperactivity in mice. Herein, we show that morphine, fentanyl, SR-17018, and oliceridine have submaximal intrinsic efficacy in the mouse striatum using 35S-GTPγS ...
Acevedo-Canabal A +7 more
europepmc +2 more sources
Physiological implications of biased signaling at histamine H2 receptors [PDF]
Frontiers in Pharmacology, 2015 Histamine mediates numerous functions acting through its four receptor subtypes all belonging to the large family of seven transmembrane G-protein coupled receptors. In particular, histamine H2 receptor (H2R) is mainly involved in gastric acid production,
Carina Shayo +6 more
core +3 more sources
Ligand recognition and biased agonism of the D1 dopamine receptor. [PDF]
Nat Commun, 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.
Teng X +6 more
europepmc +2 more sources
Biased agonism of G protein-coupled receptors as a novel strategy for osteoarthritis therapy. [PDF]
Bone ResOsteoarthritis (OA) is a prevalent degenerative joint disorder marked by chronic pain, inflammation, and cartilage loss, with current treatments limited to symptom relief.
Meng X, Qin L, Wang X.
europepmc +2 more sources
Recent updates on GPCR biased agonism [PDF]
Pharmacological Research, 2016 G protein-coupled receptors (GPCRs) are the most important targets for drug discovery and not surprisingly ∼40% of all drugs currently in the market act on these receptors. Currently, one of the most active areas in GPCRs signaling is biased agonism, a phenomenon that occurs when a given ligand is able to preferentially activate one (or some) of the ...
André S. Pupo +5 more
openaire +5 more sources
Gating Mechanism for Biased Agonism at Angiotensin II Type 1 Receptors. [PDF]
MoleculesFor the interaction of angiotensin II (AngII) with AngII type 1 receptors (AT1R), two potential proton hopping pathways have been identified, each associated with distinct physiological outcomes.
Moore GJ +5 more
europepmc +2 more sources
Allosteric coupling and biased agonism in G protein‐coupled receptors [PDF]
The FEBS Journal, 2021 G protein‐coupled receptors (GPCRs) are essential cell membrane signaling molecules and represent the most important class of drug targets. Some signaling pathways downstream of a GPCR may be responsible for drug adverse effects, while others mediate therapeutic efficacy.
Andreas Bock, Marcel Bermudez
openaire +5 more sources
Structural basis of protease-activated receptor 2 activation and biased agonism. [PDF]
Cell DiscovProtease-activated receptor 2 (PAR2) is a transmembrane receptor that is irreversibly activated by proteolytic cleavage of its N-terminus via extracellular proteases, resulting in the release of the tethered ligand (TL), which binds to and activates the ...
Zhu X +5 more
europepmc +2 more sources
G Protein-coupled Receptor Biased Agonism. [PDF]
J Cardiovasc Pharmacol, 2016 G protein-coupled receptors are the largest family of targets for current therapeutics. The classic model of their activation was binary, where agonist binding induced an active conformation and subsequent downstream signaling. Subsequently, the revised concept of biased agonism emerged, where different ligands at the same G protein-coupled receptor ...
Hodavance SY +3 more
europepmc +4 more sources