ArticleThe Journal of clinical investigation2023
Bi-steric mTORC1 inhibitors induce apoptotic cell death in tumor models with hyperactivated mTORC1.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Macropinocytosis inhibition attenuates profibrotic responses in lung fibroblasts and pulmonary fibrosis models.The Journal of clinical investigation · 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
- 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
- Mitochondrial metabolic rewiring sensitizes mTORC1 inhibitor persister cells to cuproptosis.JCI insight · 2025Article
- The Bi-steric Inhibitor RMC-5552 Reduces mTORC1 Signaling and Growth in Lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2025Article
- Plasmacytoid Dendritic Cells: Bring a Glimmer of Hope for Patients with Lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2024Article
- Preclinical evaluation of the third-generation, bi-steric mechanistic target of rapamycin complex 1-selective inhibitor RMC-6272 inNeuro-oncology advancesArticle
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The PI3K/AKT/mTOR pathway is commonly dysregulated in cancer. Rapalogs exhibit modest clinical benefit, likely owing to their lack of effects on 4EBP1. We hypothesized that bi-steric mTORC1-selective inhibitors would have greater potential for clinical benefit than rapalogs in tumors with mTORC1 dysfunction. We assessed this hypothesis in tumor models with high mTORC1 activity both in vitro and in vivo. Bi-steric inhibitors had strong growth inhibition, eliminated phosphorylated 4EBP1, and induced more apoptosis than rapamycin or MLN0128. Multiomics analysis showed extensive effects of the bi-steric inhibitors in comparison with rapamycin. De novo purine synthesis was selectively inhibited by bi-sterics through reduction in JUN and its downstream target PRPS1 and appeared to be the cause of apoptosis. Hence, bi-steric mTORC1-selective inhibitors are a therapeutic strategy to treat tumors driven by mTORC1 hyperactivation.
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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.