ArticlePloS one2013
Re-directing an alkylating agent to mitochondria alters drug target and cell death mechanism.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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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.
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.
Who cites it
9 citing papers in PubMed, 39 citations in OpenAlex.
- Mitochondria-Targeted Temozolomide Probe for Overcoming MGMT-Mediated Resistance in Glioblastoma.Chembiochem : a European journal of chemical biology · 2025Article
- Recent Advancements in Mitochondria-Targeted Nanoparticle Drug Delivery for Cancer Therapy.Nanomaterials (Basel, Switzerland) · 2022Review
- Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes: current strategies and future perspectives.Acta pharmaceutica Sinica. B · 2018Review
- Mitochondrial-Targeting Anticancer Agent Conjugates and Nanocarrier Systems for Cancer Treatment.Frontiers in pharmacology · 2018Review
- Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications.Chemical reviews · 2017Review
- Mitochondria-penetrating peptides conjugated to desferrioxamine as chelators for mitochondrial labile iron.PloS one · 2017Article
- Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes.Nature chemical biology · 2016Article
- Massive Bioaccumulation and Self-Assembly of Phenazine Compounds in Live Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2015Article
- Targeting mitochondrial DNA with a platinum-based anticancer agent.Chemistry & biology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
We have successfully delivered a reactive alkylating agent, chlorambucil (Cbl), to the mitochondria of mammalian cells. Here, we characterize the mechanism of cell death for mitochondria-targeted chlorambucil (mt-Cbl) in vitro and assess its efficacy in a xenograft mouse model of leukemia. Using a ρ° cell model, we show that mt-Cbl toxicity is not dependent on mitochondrial DNA damage. We also illustrate that re-targeting Cbl to mitochondria results in a shift in the cell death mechanism from apoptosis to necrosis, and that this behavior is a general feature of mitochondria-targeted Cbl. Despite the change in cell death mechanisms, we show that mt-Cbl is still effective in vivo and has an improved pharmacokinetic profile compared to the parent drug. These findings illustrate that mitochondrial rerouting changes the site of action of Cbl and also alters the cell death mechanism drastically without compromising in vivo efficacy. Thus, mitochondrial delivery allows the exploitation of Cbl as a promiscuous mitochondrial protein inhibitor with promising therapeutic potential.
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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 OpenQuestion graph.