ArticleChemMedChem2014
Discovery, synthesis and characterization of a highly muscarinic acetylcholine receptor (mAChR)-selective M5-orthosteric antagonist, VU0488130 (ML381): a novel molecular probe.
Article in ChemMedChem, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- The Novel Functions of M4 Muscarinic Receptors.Physiological research · 2025Review
- Development of VU6036864: A Triazolopyridine-Based High-Quality Antagonist Tool Compound of the MJournal of medicinal chemistry · 2024Article
- Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders.Annual review of pharmacology and toxicology · 2024Review
- Discovery of a potent MBioorganic & medicinal chemistry letters · 2022Article
- Discovery of a potent MBioorganic & medicinal chemistry letters · 2022Article
- Multitargeting nature of muscarinic orthosteric agonists and antagonists.Frontiers in physiology · 2022Review
- Molecular pharmacology of metabotropic receptors targeted by neuropsychiatric drugs.Nature structural & molecular biology · 2019Review
- Discovery and Optimization of Potent and CNS Penetrant MACS chemical neuroscience · 2018Article
- A Simple Representation of Three-Dimensional Molecular Structure.Journal of medicinal chemistry · 2017Article
- Discovery and optimization of 3-(4-aryl/heteroarylsulfonyl)piperazin-1-yl)-6-(piperidin-1-yl)pyridazines as novel, CNS penetrant pan-muscarinic antagonists.Bioorganic & medicinal chemistry letters · 2017Article
- All muscarinic acetylcholine receptors (MScientific reports · 2017Article
- Synthesis and evaluation of 4,6-disubstituted pyrimidines as CNS penetrant pan-muscarinic antagonists with a novel chemotype.Bioorganic & medicinal chemistry letters · 2017Article
- Continued optimization of the MBioorganic & medicinal chemistry letters · 2017Article
- Ligand-based virtual screen for the discovery of novel M5 inhibitor chemotypes.Bioorganic & medicinal chemistry letters · 2016Article
- Application of Parallel Multiparametric Cell-Based FLIPR Detection Assays for the Identification of Modulators of the Muscarinic Acetylcholine Receptor 4 (M4).Journal of biomolecular screening · 2015Article
- Further optimization of the M5 NAM MLPCN probe ML375: tactics and challenges.Bioorganic & medicinal chemistry letters · 2015Article
- Current approaches for the discovery of drugs that deter substance and drug abuse.Expert opinion on drug discovery · 2014Review
- Development of a highly potent, novel M5 positive allosteric modulator (PAM) demonstrating CNS exposure: 1-((1H-indazol-5-yl)sulfoneyl)-N-ethyl-N-(2-(trifluoromethyl)benzyl)piperidine-4-carboxamide (ML380).Journal of medicinal chemistry · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Of the five G-protein-coupled muscarinic acetylcholine receptors (mAChRs; M1-M5), M5 is the least explored and understood due to a lack of mAChR subtype-selective ligands. We recently performed a high-throughput functional screen and identified a number of weak antagonist hits that are selective for the M5 receptor. Here, we report an iterative parallel synthesis and detailed molecular pharmacologic profiling effort that led to the discovery of the first highly selective, central nervous system (CNS)-penetrant M5-orthosteric antagonist, with sub-micromolar potency (hM5 IC50=450 nM, hM5 Ki=340 nM, M1-M4 IC50>30 μM), enantiospecific inhibition, and an acceptable drug metabolism and pharmacokinetics (DMPK) profile for in vitro and electrophysiology studies. This compound will be a powerful tool and molecular probe for the further investigation into the role of M5 in addiction and other diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.