ArticleProceedings of the National Academy of Sciences of the United States of America2018
Structure-guided development of selective M3 muscarinic acetylcholine receptor antagonists.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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Who cites it
50 citing papers in PubMed.
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- Docking of virtual libraries identifies small-molecule agonists of neurotensin receptors with analgesic activity.Nature communications · 2026Article
- Tropanes in natural products, syntheses, and drugs: some insights from the new millennium.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- An in vitro mechanistic study of cholinergic-associated mechanisms relevant to MASLD in HepG2 cells.Turkish journal of biology = Turk biyoloji dergisi · 2026Article
- Chlorogenic acid reduces Lipopolysaccharide-Induced intestinal inflammation through Inhibition of acetylcholinesterase and activation of muscarinic receptors.Molecular biology reports · 2025Article
- Epoxy tetrahydrophthalimides as potential bioactive agents: synthesis and computational study.Pest management science · 2025Article
- Adiabatic-Bias Molecular Dynamics Simulations Reveal the Impact of Mutations on Muscarinic Antagonist Unbinding Kinetics.Journal of chemical information and modeling · 2025Article
- Development of Mutant MBiochemistry · 2025Article
- Research progress in myocardial function and diseases related to muscarinic acetylcholine receptor (Review).International journal of molecular medicine · 2025Review
- Design, Synthesis, and Characterization of New δ Opioid Receptor-Selective Fluorescent Probes and Applications in Single-Molecule Microscopy of Wild-Type Receptors.Journal of medicinal chemistry · 2024Article
- Further investigations on the influence of protein phosphatases on the signaling of muscarinic receptors in the atria of mouse hearts.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- G Protein-Coupled Receptor-Ligand Pose and Functional Class Prediction.International journal of molecular sciences · 2024Article
- G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.Signal transduction and targeted therapy · 2024Review
- Deepening insights into cholinergic agents for intraocular pressure reduction: systems genetics, molecular modeling, andFrontiers in molecular biosciences · 2024Article
- Exploring the Antidiarrheal Properties of Papaya Leaf: InsightsScientifica · 2024Article
- Toward high-resolution modeling of small molecule-ion channel interactions.Frontiers in pharmacology · 2024Article
- Xanomeline displays concomitant orthosteric and allosteric binding modes at the MNature communications · 2023Article
- A Novel "Activation Switch" Motif Common to All Aminergic Receptors.Journal of chemical information and modeling · 2023Review
- Unbinding Kinetics of Muscarinic M3 Receptor Antagonists Explained by Metadynamics Simulations.Journal of chemical information and modeling · 2023Article
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
Drugs that treat chronic obstructive pulmonary disease by antagonizing the M3 muscarinic acetylcholine receptor (M3R) have had a significant effect on health, but can suffer from their lack of selectivity against the M2R subtype, which modulates heart rate. Beginning with the crystal structures of M2R and M3R, we exploited a single amino acid difference in their orthosteric binding pockets using molecular docking and structure-based design. The resulting M3R antagonists had up to 100-fold selectivity over M2R in affinity and over 1,000-fold selectivity in vivo. The crystal structure of the M3R-selective antagonist in complex with M3R corresponded closely to the docking-predicted geometry, providing a template for further optimization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.