ArticleNature communications2018
A small molecule inhibitor of Rheb selectively targets mTORC1 signaling.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 96 citations in OpenAlex.
- Genotype-Phenotype Correlation in Tuberous Sclerosis Complex: Insights from North MacedoniaBalkan medical journal · 2026Article
- RagC and Map4K3 deficiency in high-grade gliomas drives proliferation and modulates mTORC1-dependent cellular functions.Journal of neuropathology and experimental neurology · 2026Article
- Bench to bedside: is rapamycin headed for the docTOR?GeroScience · 2026Review
- Covalent modification of a glutamic acid inspired by HaloTag technology.Nature communications · 2026Article
- Rheb1 signaling and the fate of pancreatic β cells: Toward a new frontier in diabetes therapy.World journal of diabetes · 2025Article
- Rheb1 as a novel β-cell regulator connecting mTORC1, AMPK, and NOTCH1 pathways for efficient diabetes therapy.World journal of diabetes · 2025Article
- TNFAIP8L2 maintains hair cell function and regulates age-related hearing loss via mTORC1 signaling.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Enolase and 16.5-kDa Tegument-Associated Protein inJournal of extracellular biology · 2025Article
- From Molecular Therapies to Lysosomal Transplantation and Targeted Drug Strategies: Present Applications, Limitations, and Future Prospects of Lysosomal Medications.Biomolecules · 2025Review
- mTORC1-selective inhibitors rescue cellular phenotypes in TSC iPSC-derived neurons.Frontiers in neuroscience · 2025Article
- Spatial and functional separation of mTORC1 signalling in response to different amino acid sources.Nature cell biology · 2024Article
- Review
- Glucose deprivation triggers DCAF1-mediated inactivation of Rheb-mTORC1 and promotes cancer cell survival.Cell death & disease · 2024Article
- mTORC1 in energy expenditure: consequences for obesity.Nature reviews. Endocrinology · 2024Review
- Article
- Unraveling the Role of Ras Homolog Enriched in Brain (Rheb1 and Rheb2): Bridging Neuronal Dynamics and Cancer Pathogenesis through Mechanistic Target of Rapamycin Signaling.International journal of molecular sciences · 2024Review
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Malonyl-CoA is a conserved endogenous ATP-competitive mTORC1 inhibitor.Nature cell biology · 2023Article
- STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway.Molecular cancer · 2023Article
- Targeting the biology of aging with mTOR inhibitors.Nature aging · 2023Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The small G-protein Rheb activates the mechanistic target of rapamycin complex 1 (mTORC1) in response to growth factor signals. mTORC1 is a master regulator of cellular growth and metabolism; aberrant mTORC1 signaling is associated with fibrotic, metabolic, and neurodegenerative diseases, cancers, and rare disorders. Point mutations in the Rheb switch II domain impair its ability to activate mTORC1. Here, we report the discovery of a small molecule (NR1) that binds Rheb in the switch II domain and selectively blocks mTORC1 signaling. NR1 potently inhibits mTORC1 driven phosphorylation of ribosomal protein S6 kinase beta-1 (S6K1) but does not inhibit phosphorylation of AKT or ERK. In contrast to rapamycin, NR1 does not cause inhibition of mTORC2 upon prolonged treatment. Furthermore, NR1 potently and selectively inhibits mTORC1 in mouse kidney and muscle in vivo. The data presented herein suggest that pharmacological inhibition of Rheb is an effective approach for selective inhibition of mTORC1 with therapeutic potential.
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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.