ArticleOncotarget2015
Structurally diverse c-Myc inhibitors share a common mechanism of action involving ATP depletion.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 42 citations in OpenAlex.
- MYC Binding Near Transcriptional End Sites Regulates Basal Gene Expression, Read-Through Transcription, and Intragenic Contacts.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Impaired mitochondrial metabolism is a critical cancer vulnerability for MYC inhibitors.Science advances · 2025Article
- Razing the scaffolding: the elimination of non-catalytic functions of kinases through targeted protein degradation.RSC medicinal chemistry · 2025Review
- Body-Wide Inactivation of the Myc-Like Mlx Transcription Factor Network Accelerates Aging and Increases the Lifetime Cancer Incidence.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Bioinformatic analysis of hippocampal histopathology in Alzheimer's disease and the therapeutic effects of active components of traditional Chinese medicine.Frontiers in pharmacology · 2024Article
- Nilotinib: Disrupting the MYC-MAX Heterocomplex.Bioinformatics and biology insights · 2024Article
- The Myc-Like Mlx Network Impacts Aging and Metabolism.bioRxiv : the preprint server for biology · 2023Article
- Premature aging and reduced cancer incidence associated with near-complete body-wide Myc inactivation.Cell reports · 2023Article
- Cytoprotective, Cytotoxic and Cytostatic Roles of Autophagy in Response to BET Inhibitors.International journal of molecular sciences · 2023Review
- Disruption of Multiple Overlapping Functions Following Stepwise Inactivation of the Extended Myc Network.Cells · 2022Article
- Regulation of Normal and Neoplastic Proliferation and Metabolism by the Extended Myc Network.Cells · 2022Review
- Coordinated Cross-Talk Between the Myc and Mlx Networks in Liver Regeneration and Neoplasia.Cellular and molecular gastroenterology and hepatology · 2022Article
- Review
- EPHB4 inhibition activates ER stress to promote immunogenic cell death of prostate cancer cells.Cell death & disease · 2019Article
- Enhancing tetrandrine cytotoxicity in human lung carcinoma A549 cells by suppressing mitochondrial ATP production.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- The BET Bromodomain Inhibitor I-BET-151 Induces Structural and Functional Alterations of the Heart Mitochondria in Healthy Male Mice and Rats.International journal of molecular sciences · 2019Article
- MTOR-independent autophagy induced by interrupted endoplasmic reticulum-mitochondrial CaAutophagy · 2019Article
- Article
- Therapeutic Inhibition of Myc in Cancer. Structural Bases and Computer-Aided Drug Discovery Approaches.International journal of molecular sciences · 2018Review
- Myc and ChREBP transcription factors cooperatively regulate normal and neoplastic hepatocyte proliferation in mice.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The c-Myc (Myc) oncoprotein is deregulated in a large proportion of diverse human cancers. Considerable effort has therefore been directed at identifying pharmacologic inhibitors as potential anti-neoplastic agents. Three such groups of small molecule inhibitors have been described. The first is comprised of so-called "direct" inhibitors, which perturb Myc's ability to form productive DNA-binding heterodimers in association with its partner, Max. The second group is comprised of indirect inhibitors, which largely function by targeting the BET-domain protein BRD4 to prevent the proper formation of transcriptional complexes that assemble in response to Myc-Max DNA binding. Thirdly, synthetic lethal inhibitors cause the selective apoptosis of Myc over-expressing either by promoting mitotic catastrophe or altering Myc protein stability. We report here a common mechanism by which all Myc inhibitors, irrespective of class, lead to eventual cellular demise. This involves the depletion of ATP stores due to mitochondrial dysfunction and the eventual down-regulation of Myc protein. The accompanying metabolic de-regulation causes neutral lipid accumulation, cell cycle arrest, and an attempt to rectify the ATP deficit by up-regulating AMP-activated protein kinase (AMPK). These responses are ultimately futile due to the lack of functional Myc to support the requisite anabolic response. Finally, the effects of Myc depletion on ATP levels, cell cycle arrest, differentiation and AMPK activation can be mimicked by pharmacologic inhibition of the mitochondrial electron transport chain without affecting Myc levels. Thus, all Myc inhibitors promote a global energy collapse that appears to underlie many of their phenotypic consequences.
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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.