ArticleNature chemical biology2021
Selective inhibitors of mTORC1 activate 4EBP1 and suppress tumor growth.
Article in Nature chemical biology, 2021. 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 48 papers.
What it found
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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.
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
48 citing papers in PubMed, 76 citations in OpenAlex.
- Rhizoma Dioscoreae Nipponicae attenuates airway remodeling and angiogenesis-related changes in asthma with altered mTOR/4EBP1/HIF-1α/VEGF pathway markers.The World Allergy Organization journal · 2026Article
- RMC-6272, a selective third-generation bi-steric mTORC1 inhibitor, improves cardiac function in pressure overload-induced cardiac hypertrophy.Journal of molecular and cellular cardiology plus · 2026Article
- 4E-BP1 acts as a molecular rheostat balancing regenerative healing and fibrotic scarring.Experimental & molecular medicine · 2026Article
- Mitochondrial ETF insufficiency drives neoplastic growth by selectively optimizing cancer bioenergetics.eLife · 2026Article
- mTORC1 activity suppresses ferroptosis through a SCARB1-dependent HDL-tocopherol uptake pathway.Molecular cell · 2026Article
- Antibody-Drug Conjugates Targeting Resistance-Associated Signaling Pathways: Recent Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- Deciphering molecular pathways in urological cancers: A gateway to precision therapeutics.Journal of advanced research · 2026Review
- Rewiring of host cell signaling in chikungunya virus infection: a mechanism for pathogenesis and therapeutic approaches.Archives of microbiology · 2026Review
- The mechanism of the PI3K-AKT-mTOR signaling pathway in renal cell carcinoma: current developments and future prospects.Frontiers in oncology · 2026Review
- Effects of miR-451 on the proliferation, invasion and migration of papillary thyroid cancer cell line TPC-1 by regulating the PI3K/AKT/mTOR signaling pathway.Endocrine connections · 2026Article
- The Bi-steric, mTORC1-Selective Inhibitor, RMC-5552, in Advanced Solid Tumors: A Phase 1 Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Article
- Dual Inhibition of CDK4/6 and mTORC1 Establishes a Preclinical Strategy for Translocation Renal Cell Carcinoma.bioRxiv : the preprint server for biology · 2025Article
- The Bi-steric Inhibitor RMC-5552 Reduces mTORC1 Signaling and Growth in Lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2025Article
- Melatonin enhances everolimus efficacy in breast cancer by suppressing mTOR pathway activation and promoting apoptosis and mitochondrial function.BMC pharmacology & toxicology · 2025Article
- Substituents introduction of methyl and methoxy functional groups on resveratrol stabilizes mTOR binding for autophagic cell death induction.Scientific reports · 2025Article
- Anticancer Potential of Prebiotics: Targeting Estrogen Receptors and PI3K/AKT/mTOR in Breast Cancer.Biomedicines · 2025Review
- Targeting Smurf1 to block PDK1-Akt signaling in KRAS-mutated colorectal cancer.Nature chemical biology · 2025Article
- Article
- From Subtypes to Solutions: Integrating CMS Classification with Precision Therapeutics in Colorectal Cancer.Current treatment options in oncology · 2024Review
Corrections and comments
- Commented on by
- Erratum issued
- Erratum issued
Authors and funding
26 authors at 5 institutions in 3 countries.
Funding
Abstract
The clinical benefits of pan-mTOR active-site inhibitors are limited by toxicity and relief of feedback inhibition of receptor expression. To address these limitations, we designed a series of compounds that selectively inhibit mTORC1 and not mTORC2. These 'bi-steric inhibitors' comprise a rapamycin-like core moiety covalently linked to an mTOR active-site inhibitor. Structural modification of these components modulated their affinities for their binding sites on mTOR and the selectivity of the bi-steric compound. mTORC1-selective compounds potently inhibited 4EBP1 phosphorylation and caused regressions of breast cancer xenografts. Inhibition of 4EBP1 phosphorylation was sufficient to block cancer cell growth and was necessary for maximal antitumor activity. At mTORC1-selective doses, these compounds do not alter glucose tolerance, nor do they relieve AKT-dependent feedback inhibition of HER3. Thus, in preclinical models, selective inhibitors of mTORC1 potently inhibit tumor growth while causing less toxicity and receptor reactivation as compared to pan-mTOR inhibitors.
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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.