ArticleJournal of medicinal chemistry2018
Discovery of Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT).
Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.
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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.
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Who cites it
37 citing papers in PubMed, 69 citations in OpenAlex.
- Efficacious Anti-Cancer Drugs Targeting NicotinamidePharmaceuticals (Basel, Switzerland) · 2026Article
- Nicotinamide N-Methyltransferase in Cardiovascular Diseases: Metabolic Regulator and Emerging Therapeutic Target.Biomolecules · 2025Review
- Article
- Nicotinamide N-Methyltransferase (NNMT) and Liver Cancer: From Metabolic Networks to Therapeutic Targets.Biomolecules · 2025Review
- Review
- Exploring NNMT: from metabolic pathways to therapeutic targets.Archives of pharmacal research · 2024Review
- Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome.Frontiers in pharmacology · 2024Review
- Ligand-based in silico identification and biological evaluation of potential inhibitors of nicotinamide N-methyltransferase.Molecular diversity · 2023Article
- Nicotinamide N-methyltransferase (NNMT) regulates the glucocorticoid signaling pathway during the early phase of adipogenesis.Scientific reports · 2023Article
- Structure-Activity Relationship Studies of Venglustat on NTMT1 Inhibition.Journal of medicinal chemistry · 2023Article
- Article
- Novel tricyclic small molecule inhibitors of Nicotinamide N-methyltransferase for the treatment of metabolic disorders.Scientific reports · 2022Article
- NicotinamideBiomolecules · 2022Review
- Exploring Unconventional SAM Analogues To Build Cell-Potent Bisubstrate Inhibitors for Nicotinamide N-Methyltransferase.Angewandte Chemie (International ed. in English) · 2022Article
- Complex roles of nicotinamide N-methyltransferase in cancer progression.Cell death & disease · 2022Review
- Nicotinamide N-Methyltransferase: A Promising Biomarker and Target for Human Cancer Therapy.Frontiers in oncology · 2022Review
- Macrocyclic peptides as allosteric inhibitors of nicotinamideRSC chemical biology · 2021Article
- Probing the SAM Binding Site of SARS-CoV-2 Nsp14 In Vitro Using SAM Competitive Inhibitors Guides Developing Selective Bisubstrate Inhibitors.SLAS discovery : advancing life sciences R & D · 2021Article
- NicotinamideBiomolecules · 2021Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of pyridine-containing compounds using the cofactor S-5'-adenosyl-l-methionine (SAM) as the methyl group donor. Through the regulation of the levels of its substrates, cofactor, and products, NNMT plays an important role in physiology and pathophysiology. Overexpression of NNMT has been implicated in various human diseases. Potent and selective small-molecule NNMT inhibitors are valuable chemical tools for testing biological and therapeutic hypotheses. However, very few NNMT inhibitors have been reported. Here, we describe the discovery of a bisubstrate NNMT inhibitor MS2734 (6) and characterization of this inhibitor in biochemical, biophysical, kinetic, and structural studies. Importantly, we obtained the first crystal structure of human NNMT in complex with a small-molecule inhibitor. The structure of the NNMT-6 complex has unambiguously demonstrated that 6 occupied both substrate and cofactor binding sites. The findings paved the way for developing more potent and selective NNMT inhibitors in the future.
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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.