ArticleJournal of pineal research2020
Structural characterization of melatonin as an inhibitor of the Wnt deacylase Notum.
Article in Journal of pineal research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- High-efficient discovering the potent anti-Notum agents from herbal medicines for combating glucocorticoid-induced osteoporosis.Acta pharmaceutica Sinica. B · 2025Article
- Melatonin as an Alleviator in Decabromodiphenyl Ether-Induced Aberrant Hippocampal Neurogenesis and Synaptogenesis: The Role of Wnt7a.Biomolecules · 2025Article
- Melatonin-A Powerful Antioxidant in Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Comprehensive investigation of multiple targets in the development of newer drugs for the Alzheimer's disease.Acta pharmaceutica Sinica. B · 2025Review
- Notum enhances gastric cancer stem-like cell properties through upregulation of Sox2 by PI3K/AKT signaling pathway.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells.Scientific reports · 2023Article
- Structural Analysis and Development of Notum Fragment Screening Hits.ACS chemical neuroscience · 2022Article
- Design of a Potent, Selective, and Brain-Penetrant Inhibitor of Wnt-Deactivating Enzyme Notum by Optimization of a Crystallographic Fragment Hit.Journal of medicinal chemistry · 2022Article
- Notum palmitoleoyl-protein carboxylesterase regulates Fas cell surface death receptor-mediated apoptosis via the Wnt signaling pathway in colon adenocarcinoma.Bioengineered · 2021Article
- Structural Insights into Notum Covalent Inhibition.Journal of medicinal chemistry · 2021Article
- A systematic summary of survival and death signalling during the life of hair follicle stem cells.Stem cell research & therapy · 2021Review
- Review
- Small-molecule inhibitors of carboxylesterase Notum.Future medicinal chemistry · 2021Review
- Carboxylesterase Notum Is a Druggable Target to Modulate Wnt Signaling.Journal of medicinal chemistry · 2021Article
- Lower Plasma Melatonin in the Intervertebral Disk Degeneration Patients Was Associated with Increased Proinflammatory Cytokines.Clinical interventions in aging · 2021Article
- Structural characterization of melatonin as an inhibitor of the Wnt deacylase Notum.Journal of pineal research · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The hormone melatonin, secreted from the pineal gland, mediates multiple physiological effects including modulation of Wnt/β-catenin signalling. The Wnt palmitoleate lipid modification is essential for its signalling activity, while the carboxylesterase Notum can remove the lipid from Wnt and inactivate it. Notum enzyme inhibition can therefore upregulate Wnt signalling. While searching for Notum inhibitors by crystallographic fragment screening, a hit compound N-[2-(5-fluoro-1H-indol-3-yl)ethyl]acetamide that is structurally similar to melatonin came to our attention. We then soaked melatonin and its precursor N-acetylserotonin into Notum crystals and obtained high-resolution structures (≤1.5 Å) of their complexes. In each of the structures, two compound molecules bind with Notum: one at the enzyme's catalytic pocket, overlapping the space occupied by the acyl tail of the Wnt palmitoleate lipid, and the other at the edge of the pocket opposite the substrate entrance. Although the inhibitory activity of melatonin shown by in vitro enzyme assays is low (IC
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