ArticleCancer letters2017
AG311, a small molecule inhibitor of complex I and hypoxia-induced HIF-1α stabilization.
Article in Cancer letters, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Mitochondrial Energy Metabolism in Cancer, Immunoregulation and Antitumour Response.Advances in experimental medicine and biology · 2026Review
- Therapeutic modulation of ROCK overcomes metabolic adaptation of cancer cells to OXPHOS inhibition and drives synergistic anti-tumor activity.bioRxiv : the preprint server for biology · 2024Article
- Insights into Molecular Mechanisms of Anticancer Activity ofPlants (Basel, Switzerland) · 2024Article
- Mitochondrial UQCC3 controls embryonic and tumor angiogenesis by regulating VEGF expression.iScience · 2023Article
- A New Quinone-Based Inhibitor of Mitochondrial Complex I in D-Conformation, Producing Invasion Reduction and Sensitization to Venetoclax in Breast Cancer Cells.Antioxidants (Basel, Switzerland) · 2023Article
- Simultaneous targeting of glycolysis and oxidative phosphorylation as a therapeutic strategy to treat diffuse large B-cell lymphoma.British journal of cancer · 2022Article
- Microbiome and oral squamous cell carcinoma: a possible interplay on iron metabolism and its impact on tumor microenvironment.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2021Article
- Targeting mitochondrial ion channels for cancer therapy.Redox biology · 2021Review
- Hypoxia and Mitochondrial Dysfunction in Pregnancy Complications.Antioxidants (Basel, Switzerland) · 2021Review
- A biallelic pathogenic variant in the OGDH gene results in a neurological disorder with features of a mitochondrial disease.Journal of inherited metabolic disease · 2021Article
- The crosstalk between HIFs and mitochondrial dysfunctions in cancer development.Cell death & disease · 2021Review
- Targeting the mitochondrial trifunctional protein restrains tumor growth in oxidative lung carcinomas.The Journal of clinical investigation · 2021Article
- Why All the Fuss about Oxidative Phosphorylation (OXPHOS)?Journal of medicinal chemistry · 2020Review
- Redox Signaling from Mitochondria: Signal Propagation and Its Targets.Biomolecules · 2020Review
- Mitochondrial Dysfunction Inhibits Hypoxia-Induced HIF-1α Stabilization and Expression of Its Downstream Targets.Frontiers in oncology · 2020Article
- Metabolic Reprogramming in Triple-Negative Breast Cancer.Frontiers in oncology · 2020Review
- Requirement of Mitochondrial Transcription Factor A in Tissue-Resident Regulatory T Cell Maintenance and Function.Cell reports · 2019Article
- TheGenes · 2018Review
- Targeting energy metabolism to eliminate cancer cells.Cancer management and research · 2018Review
- Targeting Metabolism for Cancer Therapy.Cell chemical biology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Cancer cells have a unique metabolic profile and mitochondria have been shown to play an important role in chemoresistance, tumor progression and metastases. This unique profile can be exploited by mitochondrial-targeted anticancer therapies. A small anticancer molecule, AG311, was previously shown to possess anticancer and antimetastatic activity in two cancer mouse models and to induce mitochondrial depolarization. This study defines the molecular effects of AG311 on the mitochondria to elucidate its observed efficacy. AG311 was found to competitively inhibit complex I activity at the ubiquinone-binding site. Complex I as a target for AG311 was further established by measuring oxygen consumption rate in tumor tissue isolated from AG311-treated mice. Cotreatment of cells and animals with AG311 and dichloroacetate, a pyruvate dehydrogenase kinase inhibitor that increases oxidative metabolism, resulted in synergistic cell kill and reduced tumor growth. The inhibition of mitochondrial oxygen consumption by AG311 was found to reduce HIF-1α stabilization by increasing oxygen tension in hypoxic conditions. Taken together, these results suggest that AG311 at least partially mediates its antitumor effect through inhibition of complex I, which could be exploited in its use as an anticancer agent.
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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.