ArticleCancer cell2015
Inhibition of the Mitochondrial Protease ClpP as a Therapeutic Strategy for Human Acute Myeloid Leukemia.
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Article in Cancer cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 196 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
196citing papers in PubMed, 2 pooled it
13.1field-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
196 citing papers in PubMed, 2 syntheses or guidelines pooled it, 341 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
- A Single-Arm, Open-Label Phase II Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma.The oncologist · 2023Trial
- 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
- An adaptor for feedback regulation of heme biosynthesis by a mitochondrial protease.Science (New York, N.Y.) · 2026Article
- CLPX acquires an iron-sulfur cluster to sustain mitochondrial proteostasis in cancer cells.Nature communications · 2026Article
- Mitochondrial RNA degradation regulates differentiation, stemness, and immune sensitivity in acute myeloid leukemia.Nature communications · 2026Article
- Re-evaluating the rationale for targeting oxidative phosphorylation in acute myeloid leukemia.The Biochemical journal · 2026Review
- Pmpcb modulates zebrafish neurogenesis and stress resistance via regulating mitochondria metabolism and function.Molecular neurobiology · 2026Article
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- Loss of FBXO11 establishes a stem cell program in acute myeloid leukemia by dysregulating LONP1.The Journal of clinical investigation · 2026Article
- 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
- Dual role of HIF-1α in gliomas: enhancing COX7A2 degradation and SCAF1 expression for ATP production and tumor progression.American journal of cancer research · 2026Article
- Disrupting α-Synuclein-ClpP interaction restores mitochondrial function and attenuates neuropathology in Parkinson's disease models.Molecular neurodegeneration · 2025Article
- Utilizing nanoinducers for precision degradation of bacterial protein to mitigate antibiotic resistance.Nature communications · 2025Article
- Structural Characterization of Protein-Nucleic Acid Complexes: An Overview of the Recent Innovation in the Analytic Methods.International journal of molecular sciences · 2025Review
- Targeting the Mitochondrial Protease ClpP for Anticancer Therapy.Journal of medicinal chemistry · 2025Article
- Recent advances in the design of small molecules targeting human ClpP.Future medicinal chemistry · 2025Review
136 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
39 authors at 7 institutions in 2 countries.
Alicia ColePrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Zezhou WangPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Etienne CoyaudPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Veronique VoisinDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Marcela GrondaPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Yulia JitkovaPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Rachel MattsonPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Rose HurrenPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Sonja BabovicTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
Neil MacleanPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Ian RestallPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Xiaoming WangPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Danny V JeyarajuPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Mahadeo A SukhaiPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Swayam PrabhaPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Shaheena BashirDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Ashwin RamakrishnanPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Elisa LeungDepartment of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Yi Hua QiaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Nianxian ZhangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Kevin R CombesDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Troy KetelaDepartment of Molecular Genetics, Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON M5S 3E1, Canada.
Fengshu LinPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Walid A HouryDepartment of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Ahmed AmanDrug Discovery Program, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
Rima Al-AwarDrug Discovery Program, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Wei ZhengNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.
Erno WienholdsPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2C4, Canada.
Chang Jiang XuDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
John DickPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2C4, Canada.
Jean C Y WangPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2C4, Canada.
Jason MoffatDepartment of Molecular Genetics, Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON M5S 3E1, Canada.
Mark D MindenPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2C4, Canada.
Connie J EavesTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
Gary D BaderDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Zhenyue HaoPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Steven M KornblauDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Brian RaughtPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
Aaron D SchimmerPrincess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2C4, Canada. Electronic address: aaron.schimmer@utoronto.ca.
Princess Margaret Cancer Centre · CAUniversity of Toronto · CAThe University of Texas MD Anderson Cancer Center · USOccupational Cancer Research Centre · CAOntario Institute for Cancer Research · CAUniversity of British Columbia · CANational Center for Advancing Translational Sciences · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MDrug Repurposing Screening for Rare and Neglected DiseasesZIATR000018 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI ZHENG, WEI · 2015 to 2025
$24.6MTargeting mitochondrial protein synthesis with tigecycline for the treatment of lR01CA157456 · NCI · UNIVERSITY HEALTH NETWORK · PI SCHIMMER, AARON DAVID · 2011 to 2015
$1.1MCanadian Institutes of Health ResearchNCI NIH HHS NCI 1R01CA157456NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA157456
Abstract
From an shRNA screen, we identified ClpP as a member of the mitochondrial proteome whose knockdown reduced the viability of K562 leukemic cells. Expression of this mitochondrial protease that has structural similarity to the cytoplasmic proteosome is increased in leukemic cells from approximately half of all patients with AML. Genetic or chemical inhibition of ClpP killed cells from both human AML cell lines and primary samples in which the cells showed elevated ClpP expression but did not affect their normal counterparts. Importantly, Clpp knockout mice were viable with normal hematopoiesis. Mechanistically, we found that ClpP interacts with mitochondrial respiratory chain proteins and metabolic enzymes, and knockdown of ClpP in leukemic cells inhibited oxidative phosphorylation and mitochondrial metabolism.
Indexed as
AnimalsEndopeptidase ClpEnzyme InhibitorsHeterograftsHumansLeukemia, Myeloid, AcuteMaleMiceMice, KnockoutMice, SCIDRNA, Small InterferingClpP protein, humanEndopeptidase ClpEnzyme InhibitorsRNA, Small Interfering
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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.