ArticleMolecular cancer therapeutics2021
ONC212 is a Novel Mitocan Acting Synergistically with Glycolysis Inhibition in Pancreatic Cancer.
Article in Molecular cancer therapeutics, 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 32 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
32 citing papers in PubMed, 37 citations in OpenAlex.
- ONC201/dordaviprone for H3 K27M-mutant tumors: Discovery, mechanisms, therapeutic potential, and future directions.Genes & diseases · 2027Review
- ONC201 in combination with ATR inhibitor ceralasertib exhibits potent synergy in ovarian cancer cells.bioRxiv : the preprint server for biology · 2026Article
- Correction: ONC212 is a Novel Mitocan Acting Synergistically with Glycolysis Inhibition in Pancreatic Cancer.Molecular cancer therapeutics · 2026Article
- KATP Channel Expression Determines ONC212 Sensitivity via Mitochondrial Dysfunction and PERK/ATF4/CHOP Activation in Glioblastoma.Journal of cellular and molecular medicine · 2026Article
- Small molecule activators of the mitochondrial protease ClpP induce senescence in triple-negative breast cancer cells and sensitize cells to the Bcl-2 inhibitor venetoclax.Cell death & disease · 2026Article
- Integrated Phenotypic and Transcriptomic Profiling Positions ONC212 as a Lead Imipridone in Androgen-Independent Prostate Cancer Models.International journal of molecular sciences · 2026Article
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- Development and evaluation of mitochondria-targeted caseinolytic protease (ClpP) agonist chemical probes in in vitro breast cancer models.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Small Molecule Activators of the Mitochondrial Protease ClpP Induce Senescence in Triple-Negative Breast Cancer Cells and Sensitize Cells to the Bcl-2 Inhibitor Venetoclax.Research square · 2025Article
- Recent advances in the design of small molecules targeting human ClpP.Future medicinal chemistry · 2025Review
- Mitochondrial Protease ClpP: Cancer Marker and Drug Target.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- The interconnective role of the UPS and autophagy in the quality control of cancer mitochondria.Cellular and molecular life sciences : CMLS · 2025Review
- Reprogramming of glucose metabolism in pancreatic cancer: mechanisms, implications, and therapeutic perspectives.Frontiers in immunology · 2025Review
- Reduced EZH1/2 expression in imipridone-treated cells correlates with synergy following combinations with EZH1/2 or HDAC inhibitors in diffuse glioma and other tumors.American journal of cancer research · 2025Article
- Development of Novel Imipridones with Alkyne- and Triazole-Linked Warheads on the Tricyclic Skeleton, Showing Superior Ability to Eradicate PANC-1 and Fadu Cells Compared to ONC201.International journal of molecular sciences · 2024Article
- Imipridones inhibit tumor growth and improve survival in an orthotopic liver metastasis mouse model of human uveal melanoma.British journal of cancer · 2024Article
- Integrated stress response (ISR) activation and apoptosis through HRI kinase by PG3 and other p53 pathway-restoring cancer therapeutics.Oncotarget · 2024Article
- ONC212, alone or in synergistic conjunction with Navitoclax (ABT-263), promotes cancer cell apoptosis via unconventional mitochondrial-independent caspase-3 activation.Cell communication and signaling : CCS · 2024Article
- ONC206 targeting ClpP induces mitochondrial dysfunction and protective autophagy in hepatocellular carcinoma cells.Neoplasia (New York, N.Y.) · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
ONC212 is a fluorinated imipridone with preclinical efficacy against pancreatic and other malignancies. Although mitochondrial protease ClpP was identified as an ONC212-binding target, the mechanism leading to cancer cell death is incompletely understood. We investigated mitochondrial dysfunction and metabolic rewiring triggered by ONC212 in pancreatic cancer, a deadly malignancy with an urgent need for novel therapeutics. We found ClpP is expressed in pancreatic cancer cells and is required for ONC212 cytotoxicity. ClpX, the regulatory binding partner of ClpP, is suppressed upon ONC212 treatment. Immunoblotting and extracellular flux analysis showed ONC212 impairs oxidative phosphorylation (OXPHOS) with decrease in mitochondrial-derived ATP production. Although collapse of mitochondrial function is observed across ONC212-treated cell lines, only OXPHOS-dependent cells undergo apoptosis. Cells relying on glycolysis undergo growth arrest and upregulate glucose catabolism to prevent ERK1/2 inhibition and apoptosis. Glucose restriction or combination with glycolytic inhibitor 2-deoxy-D-glucose synergize with ONC212 and promote apoptosis
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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.