ArticleGenetics2020
Imipridone Anticancer Compounds Ectopically Activate the ClpP Protease and Represent a New Scaffold for Antibiotic Development.
Article in Genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Mechanisms of imipridones in targeting mitochondrial metabolism in cancer cells.Neuro-oncology · 2021Pooled it
- 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
- Targeting ClpP Protease: Emerging Therapeutic Strategies and Small-Molecule Modulators in Drug Discovery.Medicinal research reviews · 2026Review
- 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
- Tumor extracellular vesicle RNA profiling predicts treatment response in pediatric diffuse midline glioma.bioRxiv : the preprint server for biology · 2026Article
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- Epigenetic mechanisms and therapeutic advances in diffuse midline glioma (Review).Oncology reports · 2026Review
- A Chemical-Genetic Interaction Matrix Reveals Drug Mechanism and Genetic Architecture.bioRxiv : the preprint server for biology · 2026Article
- Recent advances in the design of small molecules targeting human ClpP.Future medicinal chemistry · 2025Review
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- The therapeutic potential of repurposed mebendazole, alone and in synergistic combination with ONC201, in the treatment of diffuse midline glioma.American journal of cancer research · 2025Article
- Structure-guided development of selective caseinolytic protease P agonists as antistaphylococcal agents.Cell reports. Medicine · 2024Article
- 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
- 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
- ESF1 and MIPEP proteins promote estrogen receptor-positive breast cancer proliferation and are associated with patient prognosis.Clinical proteomics · 2024Article
- Rational combination platform trial design for children and young adults with diffuse midline glioma: A report from PNOC.Neuro-oncology · 2024Article
- Mitochondrial regulation of GPX4 inhibition-mediated ferroptosis in acute myeloid leukemia.Leukemia · 2024Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Systematic genetic interaction profiles can reveal the mechanisms-of-action of bioactive compounds. The imipridone ONC201, which is currently in cancer clinical trials, has been ascribed a variety of different targets. To investigate the genetic dependencies of imipridone action, we screened a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) knockout library in the presence of either ONC201 or its more potent analog ONC212. Loss of the mitochondrial matrix protease CLPP or the mitochondrial intermediate peptidase MIPEP conferred strong resistance to both compounds. Biochemical and surrogate genetic assays showed that impridones directly activate CLPP and that MIPEP is necessary for proteolytic maturation of CLPP into a catalytically competent form. Quantitative proteomic analysis of cells treated with ONC212 revealed degradation of many mitochondrial as well as nonmitochondrial proteins. Prompted by the conservation of ClpP from bacteria to humans, we found that the imipridones also activate ClpP from
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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.