Evidence map›Paper›PMID 33336683›Full record

SynthesisNeuro-oncology2021

Mechanisms of imipridones in targeting mitochondrial metabolism in cancer cells.

Erin R Bonner, Sebastian M Waszak, Michael A Grotzer, Sabine Mueller, Javad Nazarian

Open access · bronzeAbstract readMeta-AnalysisReview
In one paragraph

Synthesis in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
2.6field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 67 citations in OpenAlex.

  1. Trial
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  12. Mitochondrial bioenergetics and networks in melanoma: an update.Apoptosis : an international journal on programmed cell death · 2025
    Review
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  15. Article
  16. Corrigendum to Targeting apoptotic pathways for cancer therapy.The Journal of clinical investigation · 2025
    Article
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  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 5 institutions in 3 countries.

Erin R BonnerCenter for Genetic Medicine, Children's National Health System, Washington, DC.
Sebastian M WaszakCentre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway.
Michael A GrotzerDepartment of Oncology, University Children's Hospital Zürich, Zürich, Switzerland.
Sabine MuellerDepartment of Oncology, University Children's Hospital Zürich, Zürich, Switzerland.
Javad NazarianCenter for Genetic Medicine, Children's National Health System, Washington, DC.
Children's National · USGeorge Washington University · USUniversity Children's Hospital Zurich · CHUniversity of California, San Francisco · USUniversity of Oslo · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

ONC201 is the first member of the imipridone family of anticancer drugs to enter the clinic for the treatment of diverse solid and hematologic cancers. A subset of pediatric and adult patients with highly aggressive brain tumors has shown remarkable clinical responses to ONC201, and recently, the more potent derivative ONC206 entered clinical trials as a single agent for the treatment of central nervous system (CNS) cancers. Despite the emerging clinical interest in the utility of imipridones, their exact molecular mechanisms are not fully described. In fact, the existing literature points to multiple pathways (e.g. tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) signaling, dopamine receptor antagonism, and mitochondrial metabolism) as putative drug targets. We have performed a comprehensive literature review and highlighted mitochondrial metabolism as the major target of imipridones. In support of this, we performed a meta-analysis of an ONC201 screen across 539 human cancer cell lines and showed that the mitochondrial caseinolytic protease proteolytic subunit (ClpP) is the most significant predictive biomarker of response to treatment. Herein, we summarize the main findings on the anticancer mechanisms of this potent class of drugs, provide clarity on their role, and identify clinically relevant predictive biomarkers of response.

Indexed as

Antineoplastic AgentsNeoplasmsApoptosisCell Line, TumorChildHeterocyclic Compounds, 4 or More RingsHumansImidazolesPyridinesPyrimidinesTNF-Related Apoptosis-Inducing LigandAntineoplastic AgentsHeterocyclic Compounds, 4 or More RingsImidazolesPyridinesPyrimidinesTNF-Related Apoptosis-Inducing LigandClpPimipridoneONC201ONC206ONC212

Identifiers

PMID33336683
PMCPMC8041338
OpenAlexW3115841885

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.