ArticleCancer cell2019
Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality.
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Article in Cancer cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 230 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
230citing papers in PubMed, 2 pooled it
14.4field-weighted citation impact, top 1% of its field
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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
230 citing papers in PubMed, 2 syntheses or guidelines pooled it, 342 citations in OpenAlex.
- Targeting Mitochondrial Oxidative Phosphorylation Eradicates Acute Myeloid Leukemic Stem Cells.Frontiers in oncology · 2022Pooled it
- Mechanisms of imipridones in targeting mitochondrial metabolism in cancer cells.Neuro-oncology · 2021Pooled it
- A Phase 1 Randomized Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Escalating Oral Doses of Dordaviprone and the Effects of Food on the Bioavailability of Dordaviprone in Healthy Adult Subjects.Clinical pharmacology in drug development · 2025Trial
- ACTION: a randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma.Neuro-oncology · 2024Trial
- A Single-Arm, Open-Label Phase II Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma.The oncologist · 2023Trial
- Phase II Study of ONC201 in Neuroendocrine Tumors including Pheochromocytoma-Paraganglioma and Desmoplastic Small Round Cell Tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- ONC201/dordaviprone for H3 K27M-mutant tumors: Discovery, mechanisms, therapeutic potential, and future directions.Genes & diseases · 2027Review
- Pharmacological inhibition of CLPP stabilizes LETMD1 to boost thermogenesis and alleviate obesity.Adipocyte · 2026Article
- Elucidating the Molecular Impact of DA29-Induced ClpP Chemoactivation on Mitochondrial Function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Cancer-associated mitochondrial homeostasis disrupted and retrograde signaling activated.Medical oncology (Northwood, London, England) · 2026Review
- Integrated stress response activation in combination PG3 and cisplatin-treatedbioRxiv : the preprint server for biology · 2026Article
- ONC201 enhances the radiosensitivity of small-cell lung cancer via inhibition of the FAK signaling pathway.iScience · 2026Article
- Deciphering LonP1's role in glioblastoma: an alternative mechanism of treatment resistance.American journal of physiology. Cell physiology · 2026Article
- Targeting ClpP Protease: Emerging Therapeutic Strategies and Small-Molecule Modulators in Drug Discovery.Medicinal research reviews · 2026Review
- Oncogenic DHX15 mutation enhances mitochondrial metabolism and sustains leukemia stemness.Leukemia · 2026Article
- Design, Synthesis, and Structure-Activity Relationships of Novel Piperidine-Fused Imidazolone ClpP Activators as Potential Anti-Cancer Agents.Molecules (Basel, Switzerland) · 2026Article
- TR-107, a novel mitochondrial ClpP agonist, induces robust antitumor activity against preclinical models of adrenocortical carcinoma.bioRxiv : the preprint server for biology · 2026Article
- Review
- KATP Channel Expression Determines ONC212 Sensitivity via Mitochondrial Dysfunction and PERK/ATF4/CHOP Activation in Glioblastoma.Journal of cellular and molecular medicine · 2026Article
- Target identification and assessment in the era of AI.Nature reviews. Drug discovery · 2026Review
170 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
32 authors at 5 institutions in 3 countries.
Jo IshizawaThe University of Texas MD Anderson Cancer Center, Molecular Hematology and Therapy, Department of Leukemia, Houston, TX 77030, USA.
Sarah F ZarabiPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada.
R Eric DavisThe University of Texas MD Anderson Cancer Center; Department of Lymphoma and Myeloma, Houston, TX 77030, USA.
Ondrej HalgasPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Takenobu NiiThe University of Texas MD Anderson Cancer Center, Molecular Hematology and Therapy, Department of Leukemia, Houston, TX 77030, USA.
Yulia JitkovaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Ran ZhaoThe University of Texas MD Anderson Cancer Center, Molecular Hematology and Therapy, Department of Leukemia, Houston, TX 77030, USA.
Jonathan St-GermainPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Lauren E HeeseThe University of Texas MD Anderson Cancer Center, Molecular Hematology and Therapy, Department of Leukemia, Houston, TX 77030, USA.
Grace EganPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Vivian R RuvoloThe University of Texas MD Anderson Cancer Center, Molecular Hematology and Therapy, Department of Leukemia, Houston, TX 77030, USA.
Samir H BarghoutPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada.
Yuki NishidaThe University of Texas MD Anderson Cancer Center, Molecular Hematology and Therapy, Department of Leukemia, Houston, TX 77030, USA.
Rose HurrenPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Wencai MaThe University of Texas MD Anderson Cancer Center, Bioinformatics and Comp Biology, Houston, TX 77030, USA.
Marcela GrondaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Todd LinkThe University of Texas MD Anderson Cancer Center, Genomic Medicine, Houston, TX 77030, USA.
Keith WongPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Mark MabangloDepartment of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Kensuke KojimaThe University of Texas MD Anderson Cancer Center, Molecular Hematology and Therapy, Department of Leukemia, Houston, TX 77030, USA; Saga University, Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Saga 849-8501, Japan.
Gautam BorthakurThe University of Texas MD Anderson Cancer Center, Molecular Hematology and Therapy, Department of Leukemia, Houston, TX 77030, USA.
Neil MacLeanPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Man Chun John MaThe University of Texas MD Anderson Cancer Center; Department of Lymphoma and Myeloma, Houston, TX 77030, USA.
Andrew B LeberPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Mark D MindenPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada.
Walid HouryDepartment of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada.
Hagop KantarjianThe University of Texas MD Anderson Cancer Center; Department of Leukemia, Houston, TX 77030, USA.
Martin StogniewOncoceutics, Inc., Philadelphia, PA 19104, USA.
Brian RaughtPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada.
Emil F PaiPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
Aaron D SchimmerPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada. Electronic address: aaron.schimmer@uhn.ca.
Michael AndreeffThe University of Texas MD Anderson Cancer Center, Molecular Hematology and Therapy, Department of Leukemia, Houston, TX 77030, USA; The University of Texas MD Anderson Cancer Center; Department of Leukemia, Houston, TX 77030, USA. Electronic address: mandreef@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USPrincess Margaret Cancer Centre · CAUniversity of Toronto · CAUniversity Health Network · CAOncoceutics (United States) · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MUniversity of Texas M.D. Anderson Cancer SPORE-LeukemiaP50CA100632 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KONOPLEVA, MARINA Y · 2003 to 2023
$43.7MCIHRFDA HHS R01 FD006118NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA100632
Abstract
The mitochondrial caseinolytic protease P (ClpP) plays a central role in mitochondrial protein quality control by degrading misfolded proteins. Using genetic and chemical approaches, we showed that hyperactivation of the protease selectively kills cancer cells, independently of p53 status, by selective degradation of its respiratory chain protein substrates and disrupts mitochondrial structure and function, while it does not affect non-malignant cells. We identified imipridones as potent activators of ClpP. Through biochemical studies and crystallography, we show that imipridones bind ClpP non-covalently and induce proteolysis by diverse structural changes. Imipridones are presently in clinical trials. Our findings suggest a general concept of inducing cancer cell lethality through activation of mitochondrial proteolysis.
Indexed as
AnimalsCell Line, TumorCell SurvivalCrystallography, X-RayDrug Screening Assays, AntitumorEndopeptidase ClpFemaleHCT116 CellsHEK293 CellsHeterocyclic Compounds, 4 or More RingsHumansImidazolesLeukemia, Myeloid, AcuteMiceMitochondriaModels, MolecularClpP protein, humanEndopeptidase ClpHeterocyclic Compounds, 4 or More RingsImidazolesPyridinesPyrimidinesTIC10 compoundTP53 protein, humanTumor Suppressor Protein p53acute myeloid leukemiacancerimipridonelymphomamitochondrial ClpPmitochondrial proteolysisoxidative phosphorylationrespiratory chain complex
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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.