ArticleJournal of medicinal chemistry2023
Discovery of RMC-5552, a Selective Bi-Steric Inhibitor of mTORC1, for the Treatment of mTORC1-Activated Tumors.
Article in Journal of medicinal chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- mTORC2-NaChannels (Austin, Tex.) · 2026Article
- A design approach for bitopic kinase inhibitors.Nature · 2026Article
- Emerging Strategies Targeting the PI3K/AKT/mTOR Pathway in HR+/HER2- Advanced Breast Cancer.Drugs · 2026Review
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Overcoming mTOR Inhibitor Resistance: From Biological Basis to Therapeutic Strategies.Biomedicines · 2026Review
- Macropinocytosis inhibition attenuates profibrotic responses in lung fibroblasts and pulmonary fibrosis models.The Journal of clinical investigation · 2026Article
- Bench to bedside: is rapamycin headed for the docTOR?GeroScience · 2026Review
- 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
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- mTORC1 activity suppresses ferroptosis through a SCARB1-dependent HDL-tocopherol uptake pathway.Molecular cell · 2026Article
- Unleashing lncRNA THOR: roles in cancer progression and clinical outlook.Molecular genetics and genomics : MGG · 2026Review
- Systematic and precise interventions for KRAS-mutant cancers.Experimental hematology & oncology · 2026Review
- Combining Brigatinib with mTOR Inhibition to Effectively Treat NF2-SWN-Associated and Sporadic NF2-Deficient Meningiomas.Cancer research communications · 2026Article
- Onatasertib re-sensitizes refractory nasopharyngeal carcinoma to immunotherapy: a Case Report.Frontiers in pharmacology · 2026Article
- The mechanism of the PI3K-AKT-mTOR signaling pathway in renal cell carcinoma: current developments and future prospects.Frontiers in oncology · 2026Review
- PTEN-loss confers dependence on the guanylate synthesis enzyme IMPDH in T-cell acute lymphoblastic leukemia.bioRxiv : the preprint server for biology · 2025Article
- 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
- Dual Inhibition of CDK4/6 and mTORC1 Establishes a Preclinical Strategy for Translocation Renal Cell Carcinoma.bioRxiv : the preprint server for biology · 2025Article
- Accommodating Statistical and Physics-Based Computational Protocols for Molecular Glue Model and Evaluation.Journal of chemical information and modeling · 2025Article
Corrections and comments
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Authors and funding
29 authors.
Funding
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Abstract
Hyperactivation of mTOR kinase by mutations in the PI3K/mTOR pathway or by crosstalk with other mutant cancer drivers, such as RAS, is a feature of many tumors. Multiple allosteric inhibitors of mTORC1 and orthosteric dual inhibitors of mTORC1 and mTORC2 have been developed as anticancer drugs, but their clinical utility has been limited. To address these limitations, we have developed a novel class of "bi-steric inhibitors" that interact with both the orthosteric and the allosteric binding sites in order to deepen the inhibition of mTORC1 while also preserving selectivity for mTORC1 over mTORC2. In this report, we describe the discovery and preclinical profile of the development candidate RMC-5552 and the in vivo preclinical tool compound RMC-6272. We also present evidence that selective inhibition of mTORC1 in combination with covalent inhibition of KRAS
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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.