ArticleNature communications2023
Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Multi-cell death gene signature predicts lung adenocarcinoma prognosis and reveals FURIN regulates ferroptosis via NRF2-xCT-GPX4 axis.Respiratory research · 2026Article
- Targeting ClpP Protease: Emerging Therapeutic Strategies and Small-Molecule Modulators in Drug Discovery.Medicinal research reviews · 2026Review
- Small molecule activators of the mitochondrial protease ClpP induce senescence in triple-negative breast cancer cells and sensitize cells to the Bcl-2 inhibitor venetoclax.Cell death & disease · 2026Article
- CLPX acquires an iron-sulfur cluster to sustain mitochondrial proteostasis in cancer cells.Nature communications · 2026Article
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- Cooperative Architecture of Mitochondrial Proteome Homeostasis.medRxiv : the preprint server for health sciences · 2026Article
- Activating protein kinases to treat diseases: Current understanding and future challenges.Acta pharmaceutica Sinica. B · 2026Review
- Dysregulation of human ClpP using small molecules with piperazine-based scaffold for diffuse intrinsic pontine glioma therapy validated by patient-derived tumor organoids.Research square · 2026Article
- The application of nanotechnology in regulating mitochondrial function in tumor microenvironment for cancer therapy.Theranostics · 2026Review
- Targeting lung cancer: synergistic therapeutic strategy of cuproptosis and immunogenic cell death.Frontiers in cell and developmental biology · 2026Review
- Development and evaluation of mitochondria-targeted caseinolytic protease (ClpP) agonist chemical probes in in vitro breast cancer models.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Construction and validation of an oxidative phosphorylation-related gene signature in lung squamous cell carcinoma patients.Lung cancer management · 2025Article
- Small Molecule Activators of the Mitochondrial Protease ClpP Induce Senescence in Triple-Negative Breast Cancer Cells and Sensitize Cells to the Bcl-2 Inhibitor Venetoclax.Research square · 2025Article
- Targeting the Mitochondrial Protease ClpP for Anticancer Therapy.Journal of medicinal chemistry · 2025Article
- Recent advances in the design of small molecules targeting human ClpP.Future medicinal chemistry · 2025Review
- The overexpression of HOXC6 in LUSC and pan-squamous cell carcinomas indicates the coexistence of nuclear division regulatory mechanisms.Cancer biomarkers : section A of Disease markers · 2025Article
- Mitochondrial Protease ClpP: Cancer Marker and Drug Target.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Mechanism of allosteric activation in human mitochondrial ClpP protease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Functions of the Muscleblind-like protein family and their role in disease.Cell communication and signaling : CCS · 2025Review
- Analysis and exploration of regulatory mechanisms and potential prognostic biomarkers in squamous cell carcinoma of the lung by expression profiling.Translational cancer research · 2025Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemo-activation of mitochondrial ClpP exhibits promising anticancer properties. However, we are currently unaware of any studies using selective and potent ClpP activators in lung squamous cell carcinoma. In this work, we report on such an activator, ZK53, which exhibits therapeutic effects on lung squamous cell carcinoma in vivo. The crystal structure of ZK53/ClpP complex reveals a π-π stacking effect that is essential for ligand binding selectively to the mitochondrial ClpP. ZK53 features on a simple scaffold, which is distinct from the activators with rigid scaffolds, such as acyldepsipeptides and imipridones. ZK53 treatment causes a decrease of the electron transport chain in a ClpP-dependent manner, which results in declined oxidative phosphorylation and ATP production in lung tumor cells. Mechanistically, ZK53 inhibits the adenoviral early region 2 binding factor targets and activates the ataxia-telangiectasia mutated-mediated DNA damage response, eventually triggering cell cycle arrest. Lastly, ZK53 exhibits therapeutic effects on lung squamous cell carcinoma cells in xenograft and autochthonous mouse models.
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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.