Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes [PDF]
, 2018 The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating ...
Bradley, Sophie J. +14 more
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Influence of Chemokine N-Terminal Modification on Biased Agonism at the Chemokine Receptor CCR1. [PDF]
Int J Mol Sci, 2019 Sanchez J, Lane JR, Canals M, Stone MJ.
europepmc +2 more sources
A Pharmacological Primer of Biased Agonism [PDF]
Endocrine, Metabolic & Immune Disorders - Drug Targets, 2011 Biased agonism is one of the fastest growing topics in G protein-coupled receptor pharmacology; moreover, biased agonists are used in the clinic today: carvedilol (Coreg®) is a biased agonist of beta-adrenergic receptors. However, there is a general lack of understanding of biased agonism when compared to traditional pharmacological terminology ...
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Signal Transduction and Pathogenic Modifications at the Melanocortin-4 Receptor: A Structural Perspective [PDF]
, 2019 The melanocortin-4 receptor (MC4R) can be endogenously activated by binding of melanocyte-stimulating hormones (MSH), which mediates anorexigenic effects. In contrast, the agouti-related peptide (AgRP) acts as an endogenous inverse agonist and suppresses
Biebermann, Heike +10 more
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Assessment of the molecular mechanisms of action of novel 4-phenylpyridine-2-one and 6-phenylpyrimidin-4-one allosteric modulators at the M1 muscarinic acetylcholine receptors [PDF]
, 2018 Positive allosteric modulators (PAMs) that target the M1 muscarinic acetylcholine (ACh) receptor (M1 mAChR) are potential treatments for cognitive deficits in conditions such as Alzheimer's disease and schizophrenia.
Andrew B. Tobin +15 more
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Biased Agonism: Lessons from Studies of Opioid Receptor Agonists
Annual Review of Pharmacology and Toxicology, 2023 In ligand bias different agonist drugs are thought to produce distinct signaling outputs when activating the same receptor. If these signaling outputs mediate therapeutic versus adverse drug effects, then agonists that selectively activate the therapeutic signaling pathway would be extremely beneficial.
Kelly, Eamonn +2 more
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Pepducins as a potential treatment strategy for asthma and COPD. [PDF]
, 2018 Current therapies to treat asthma and other airway diseases primarily include anti-inflammatory agents and bronchodilators. Anti-inflammatory agents target trafficking and resident immunocytes and structural cells, while bronchodilators act to prevent or
Benovic, Jeffrey L. +4 more
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Isoform-Specific Biased Agonism of Histamine H3 Receptor Agonists [PDF]
Molecular Pharmacology, 2017 The human histamine H3 receptor (hH3R) is subject to extensive gene splicing that gives rise to a large number of functional and nonfunctional isoforms. Despite the general acceptance that G protein-coupled receptors can adopt different ligand-induced conformations that give rise to biased signaling, this has not been studied for the H3R; further, it ...
Darren M, Riddy +11 more
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In vitro and in vivo pharmacological activities of 14-o-phenylpropyloxymorphone, a potent mixed mu/delta/kappa-opioid receptor agonist with reduced constipation in mice [PDF]
, 2018 Pain, particularly chronic pain, is still an unsolved medical condition. Central goals in pain control are to provide analgesia of adequate efficacy and to reduce complications associated with the currently available drugs.
Lattanzi, Roberta +4 more
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The Pathogenic TSH β-Subunit Variant C105Vfs114X Causes a Modified Signaling Profile at TSHR [PDF]
, 2019 1) Background: Central congenital hypothyroidism (CCH) is a rare endocrine disorder that can be caused by mutations in the β-subunit of thyrotropin (TSHB).
Biebermann, Heike +6 more
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