ArticleNeoplasia (New York, N.Y.)2024
ONC206 targeting ClpP induces mitochondrial dysfunction and protective autophagy in hepatocellular carcinoma cells.
Article in Neoplasia (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- ONC206 demonstrates potent antitumorigenic activity and is a potential novel therapeutic strategy for high-risk medulloblastoma.Neuro-oncology · 2026Article
- The Imipridone ONC206 Inhibits Tumor Growth and Improves Survival in Patient-Derived Xenograft Models of Uveal Melanoma.Cancers · 2026Article
- Integrated Phenotypic and Transcriptomic Profiling Positions ONC212 as a Lead Imipridone in Androgen-Independent Prostate Cancer Models.International journal of molecular sciences · 2026Article
- Preclinical efficacy of combinatorial B7-H3 CAR T cells and ONC206 against diffuse intrinsic pontine glioma.Neuro-oncology · 2026Article
- Decoding autophagy in neuro-tumor crosstalk: from underlying mechanisms to translational opportunities.Theranostics · 2026Review
- The role of mitochondrial proteases in inflammation and immunity.Frontiers in immunology · 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
- ClpP deficiency attenuates contrast-induced HK-2 cell injury through changes associated with mitochondrial dynamics and apoptosis.PloS one · 2026Article
- Mitochondrial Protease ClpP: Cancer Marker and Drug Target.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Investigating the Effects of ONC206 Alone and in Combination with Cisplatin on Ovarian Cancer Cell Models.Current issues in molecular biology · 2025Article
- ONC201 (Dordaviprone) Induces Integrated Stress Response and Death in Cervical Cancer Cells.Biomolecules · 2025Article
- Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities.Journal of translational medicine · 2025Review
- Targeting mitochondrial ClpP: structural insights and therapeutic potential of ClpP agonists in cancer therapy.Oncology reviews · 2025Review
- Targeting cell death mechanisms: the potential of autophagy and ferroptosis in hepatocellular carcinoma therapy.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for approximately 90 % of all cases. ONC201, a member of the imipridone drug family, has shown promising therapeutic potential and a good safety profile in both malignant pediatric central nervous system tumors (diffuse midline glioma [DMG]) and hematologic malignancies. ONC206 is a more potent analog of ONC201. However, the ONC206 potential and mechanism of action in HCC remain to be elucidated. We found that ONC206 hindered HCC growth by suppressing cell proliferation and inducing apoptosis. Moreover, ONC206 induced cytoprotective autophagy, and blocking autophagy enhanced the proapoptotic effect of ONC206. Additionally, ONC206 induced mitochondrial swelling, reduced the mitochondrial membrane potential (MMP), and led to the accumulation of mitochondrial ROS in HCC cells, ultimately resulting in mitochondrial dysfunction. The HCC patient samples exhibited notably elevated levels of caseinolytic protease proteolytic subunit (ClpP), which serves as a mediator of ONC206-induced mitochondrial dysfunction and the activation of protective autophagy. knockdown of ClpP reversed the cytotoxic effects of ONC206 on HCC cells. In summary, our results provide the first insight into the mechanism by which ONC206 exerts its anti-HCC effects and induces protective autophagy in HCC cells through ClpP.
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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 Socratic graph.