eLife, 2023 Allosteric modulation of G protein-coupled receptors (GPCRs) is a major paradigm in drug discovery. Despite decades of research, a molecular-level understanding of the general principles that govern the myriad pharmacological effects exerted by GPCR ...
Ziva Vuckovic +23 more
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Muscarinic Acetylcholine Receptor M4 [PDF]
Definitions, 2020 National Cancer Institute
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American Journal of Respiratory Cell and Molecular Biology, 2022 ligands, the expectation is that they will only trigger G-protein–independent pathways that promote antiremodeling and bronchorelaxant actions via b -arrestin pathways that are distinct from those driving bronchial hyperresponsiveness.
Yassine Amrani
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Postsynaptic adaptations in direct pathway muscarinic M4-receptor signaling follow the temporal and regional pattern of dopaminergic degeneration [PDF]
npj Parkinson's DiseaseIn Parkinson’s disease (PD), imbalances in dorsal striatum pathways are thought to lead to motor dysfunction due to loss of dopamine (DA) and the disruption of coordinated modulation with acetylcholine (ACh).
Beatriz E. Nielsen, Christopher P. Ford
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Detection and Quantification of Allosteric Modulation of Endogenous M4 Muscarinic Acetylcholine Receptor Using Impedance-Based Label-Free Technology in a Neuronal Cell Line [PDF]
Journal of biomolecular screening, 2014 Allosteric modulators of G protein–coupled receptors have the potential to achieve greater receptor subtype selectivity compared with ligands targeting the orthosteric site of this receptor family.
Amy N. Y. Chen +5 more
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Long-term activation upon brief exposure to xanomleline is unique to M1 and M4 subtypes of muscarinic acetylcholine receptors. [PDF]
PLoS ONE, 2014 Xanomeline is an agonist endowed with functional preference for M1/M4 muscarinic acetylcholine receptors. It also exhibits both reversible and wash-resistant binding to and activation of these receptors.
Eva Šantrůčková +3 more
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Discovery of VU6016235: A Highly Selective, Orally Bioavailable, and Structurally Distinct Tricyclic M4 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator (PAM). [PDF]
ACS Chem NeurosciHerein, we report structure–activity relationship (SAR) studies to develop novel tricyclic M4 PAM scaffolds with improved pharmacological properties. This endeavor involved a “tie-back” strategy to replace a 5-amino-2,4-dimethylthieno[2,3-d]pyrimidine-6 ...
Engers JL +17 more
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Discovery of Selective M4 Muscarinic Acetylcholine Receptor Agonists with Novel Carbamate Isosteres
ACS Medicinal Chemistry Letters, 2019 It has been hypothesized that selective muscarinic acetylcholine receptor (mAChR) M4 subtype activation could provide therapeutic benefits to a number of neurological disorders while minimizing unwanted cholinergic side effects observed due to ...
Qingyi Yang +10 more
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American Journal of Nuclear Medicine and Molecular ImagingSeveral therapeutics and biomarkers that target Alzheimer's disease (AD) are under development. Our clinical positron emission tomography (PET) research programs are interested in six radiopharmaceuticals to image patients with AD and related dementias ...
Faustine d’Orchymont
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