ArticleBiochemical pharmacology2016
Ciclopirox olamine inhibits mTORC1 signaling by activation of AMPK.
Article in Biochemical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Effect of the antifungal drug ciclopirox on the inhibition of HMGA2-mediated oncogenic capacity in ACHN renal cell carcinoma.Frontiers in pharmacology · 2026Article
- Inhibition of autophagy enhances the sensitivity of ciclopirox olamine in human chronic myelogenous leukemia K562 cells.International journal of medical sciences · 2025Article
- Article
- Ciclopirox inhibits SARS-CoV-2 replication by promoting the degradation of the nucleocapsid protein.Acta pharmaceutica Sinica. B · 2024Article
- A fragment-based drug discovery developed on ciclopirox for inhibition of Hepatitis B virus core protein: An in silico study.PloS one · 2023Article
- [Therapeutic peculiarities in diseases of the nipple skin].Dermatologie (Heidelberg, Germany) · 2022Review
- Aspiletrein A Induces Apoptosis Cell Death via Increasing Reactive Oxygen Species Generation and AMPK Activation in Non-Small-Cell Lung Cancer Cells.International journal of molecular sciences · 2022Article
- Ciclopirox Olamine Exerts Tumor-Suppressor EffectsFrontiers in oncology · 2022Article
- Breast intraductal nanoformulations for treating ductal carcinoma in situ II: Dose de-escalation using a slow releasing/slow bioconverting prodrug strategy.Drug delivery and translational research · 2022Article
- Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting the γ-secretase complex.Cell death & disease · 2021Article
- Ciclopirox olamine induces ferritinophagy and reduces cyst burden in polycystic kidney disease.JCI insight · 2021Article
- Unfolding antifungals: as a new foe to pancreatic ductal adenocarcinoma-a mini-review.Molecular biology reports · 2021Review
- Reposition of the Fungicide Ciclopirox for Cancer Treatment.Recent patents on anti-cancer drug discovery · 2021Review
- Ciclopirox activates PERK-dependent endoplasmic reticulum stress to drive cell death in colorectal cancer.Cell death & disease · 2020Article
- Iron chelation inhibits mTORC1 signaling involving activation of AMPK and REDD1/Bnip3 pathways.Oncogene · 2020Article
- Leptin: an unappreciated key player in SLE.Clinical rheumatology · 2020Review
- Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly.Nature communications · 2019Article
- Sugar and iron: Toward understanding the antibacterial effect of ciclopirox in Escherichia coli.PloS one · 2019Article
- mTORC1/2 and Protein Translation Regulate Levels of CHK1 and the Sensitivity to CHK1 Inhibitors in Ewing Sarcoma Cells.Molecular cancer therapeutics · 2018Article
- Ciclopirox activates ATR-Chk1 signaling pathway leading to Cdc25A protein degradation.Genes & cancer · 2018Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Ciclopirox olamine (CPX), an off-patent antifungal agent, has recently been identified as a potential anticancer agent. The mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation and survival. Little is known about whether and how CPX executes its anticancer action by inhibiting mTOR. Here we show that CPX inhibited the phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), two downstream effector molecules of mTOR complex 1 (mTORC1), in a spectrum of human tumor cells, indicating that CPX inhibits mTORC1 signaling. Using rhabdomyosarcoma cells as an experimental model, we found that expression of constitutively active mTOR (E2419K) conferred resistance to CPX inhibition of cell proliferation, suggesting that CPX inhibition of mTORC1 contributed to its anticancer effect. In line with this, treatment with CPX inhibited tumor growth and concurrently suppressed mTORC1 signaling in RD xenografts. Mechanistically, CPX inhibition of mTORC1 was neither via inhibition of IGF-I receptor or phosphoinositide 3-kinase (PI3K), nor by activation of phosphatase and tensin homolog (PTEN). Instead, CPX inhibition of mTORC1 was attributed to activation of AMP-activated protein kinase (AMPK)-tuberous sclerosis complexes (TSC)/raptor pathways. This is supported by the findings that CPX activated AMPK; inhibition of AMPK with Compound C or ectopic expression of dominant negative AMPKα partially prevented CPX from inhibiting mTORC1; silencing TSC2 attenuated CPX inhibition of mTORC1; and CPX also increased AMPK-mediated phosphorylation of raptor (S792). Therefore, the results indicate that CPX exerts the anticancer effect by activating AMPK, resulting in inhibition of mTORC1 signaling.
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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.