ArticleScientific reports2019
Discovery of NV-5138, the first selective Brain mTORC1 activator.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
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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.
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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
42 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Investigational Drugs for the Treatment of Depression (Part 2): Glutamatergic, Cholinergic, Sestrin Modulators, and Other Agents.Frontiers in pharmacology · 2022Pooled it
- Investigational Drugs for the Treatment of Depression (Part 1): Monoaminergic, Orexinergic, GABA-Ergic, and Anti-Inflammatory Agents.Frontiers in pharmacology · 2022Pooled it
- Unique fluoroalkyl substituents: is there life after CFChemical science · 2026Review
- Towards precision psychiatry: initial foundations and future directions.Nature reviews. Drug discovery · 2026Review
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- Driving proteomic imbalance in malignancy provokes proteomic catastrophe and confers tumor suppression.bioRxiv : the preprint server for biology · 2026Article
- Review
- A Time-Sensitive Plasticity Distinguishes the Rapid and Sustained Synaptic Actions of Ketamine from Its (2The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Allosteric Conformational Locking of Sestrin2 by Leucine: An Integrated Computational Analysis of Branched-Chain Amino Acid Recognition and Specificity.Molecules (Basel, Switzerland) · 2025Article
- The Molecular Basis of Amino Acids Sensing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Review
- Article
- Quantitative Imaging of Regional Cerebral Protein Synthesis in Clinical Alzheimer's Disease by [Molecular imaging and biology · 2024Article
- Review
- Boolean Modeling of Biological Network Applied to Protein-Protein Interaction Network of Autism Patients.Biology · 2024Article
- Sestrin2 can alleviate endoplasmic reticulum stress to improve traumatic brain injury by activating AMPK/mTORC1 signaling pathway.Metabolic brain disease · 2024Review
- Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments.Proceedings of the National Academy of Sciences of the United States of America · 2023Review
- The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease.Nature reviews. Molecular cell biology · 2023Review
- PTRH2 is Necessary for Purkinje Cell Differentiation and Survival and its Loss Recapitulates Progressive Cerebellar Atrophy and Ataxia Seen in IMNEPD Patients.Cerebellum (London, England) · 2023Article
- Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) has been linked to several important chronic medical conditions many of which are associated with advancing age. A variety of inputs including the amino acid leucine are required for full mTORC1 activation. The cytoplasmic proteins Sestrin1 and Sestrin2 specifically bind to the multiprotein complex GATOR2 and communicate leucine sufficiency to the mTORC1 pathway activation complex. Herein, we report NV-5138, a novel orally bioavailable compound that binds to Sestrin2 and activates mTORC1 both in vitro and in vivo. NV-5138 like leucine transiently activates mTORC1 in several peripheral tissues, but in contrast to leucine uniquely activates this complex in the brain due lack of metabolism and utilization in protein synthesis. As such, NV-5138 will permit the exploration in areas of unmet medical need including neuropsychiatric conditions and cognition which have been linked to the activation status of mTORC1.
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Registered trials
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