ArticleClinical cancer research : an official journal of the American Association for Cancer Research2018
The Anticancer Activity of a First-in-class Small-molecule Targeting PCNA.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Exploiting DNA damage tolerance for precision oncology.Trends in cancer · 2026Review
- Screening for novel chemical scaffolds targeting PCNA identifies the Hsp90alpha inhibitor SNX-2112.Current research in structural biology · 2026Article
- Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer.Cancer research communications · 2026Article
- Synthesis and Anticancer Evaluation of PCNA Inhibitor AOH1996 Analogs in Cancer Cell Cultures.Molecules (Basel, Switzerland) · 2026Article
- Targeting PCNA in Cancer: A Paradigm Shift from Static Inhibition to Dynamic Network Modulation.Oncology research · 2026Review
- AOH1996, an Inhibitor of PCNA, Sensitises Breast Cancer Cells to Cytotoxic Chemotherapy.Breast cancer (Dove Medical Press) · 2026Article
- Targeting DNA repair mechanisms in cancer therapy: the role of small molecule DNA repair inhibitors.NAR cancer · 2025Review
- Transforming cancer immunotherapy: integration of distinct immune-based approaches as redefined dual immunotherapy with potential third-sensitizer.Experimental hematology & oncology · 2025Review
- Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.Frontiers in pharmacology · 2025Review
- Targeting PCNA/PARP1 axis inhibits the malignant progression of hepatocellular carcinoma.Frontiers in pharmacology · 2025Article
- AOH1996 targets mitochondrial dynamics and metabolism in leukemic stem cells via mitochondrial PCNA inhibition.Experimental hematology & oncology · 2024Article
- Identification of functional circRNAs regulating ovarian follicle development in goats.BMC genomics · 2024Article
- Review
- Kaempferol Alleviates Hepatic Injury in Nonalcoholic Steatohepatitis (NASH) by Suppressing Neutrophil-Mediated NLRP3-ASC/TMS1-Caspase 3 Signaling.Molecules (Basel, Switzerland) · 2024Article
- The potential of PCNA inhibition as a therapeutic strategy in cervical cancer.Journal of medical virology · 2023Review
- NKp44-Derived Peptide Used in Combination Stimulates Antineoplastic Efficacy of Targeted Therapeutic Drugs.International journal of molecular sciences · 2022Article
- Review
- Epigallocatechin-3-gallate suppresses the growth of human osteosarcoma by inhibiting the Wnt/β-catenin signalling pathway.Bioengineered · 2022Article
- Proliferating cell nuclear antigen directly interacts with androgen receptor and enhances androgen receptor‑mediated signaling.International journal of oncology · 2021Article
- Targeting Non-Oncogene Addiction for Cancer Therapy.Biomolecules · 2021Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
purposeProliferating cell nuclear antigen (PCNA) plays an essential role in regulating DNA synthesis and repair and is indispensable to cancer cell growth and survival. We previously reported a novel cancer associated PCNA isoform (dubbed caPCNA), which was ubiquitously expressed in a broad range of cancer cells and tumor tissues, but not significantly in nonmalignant cells. We found the L126-Y133 region of caPCNA is structurally altered and more accessible to protein-protein interaction. A cell-permeable peptide harboring the L126-Y133 sequence blocked PCNA interaction in cancer cells and selectively kills cancer cells and xenograft tumors. On the basis of these findings, we sought small molecules targeting this peptide region as potential broad-spectrum anticancer agents. EXPERIMENTAL
designBy computer modeling and medicinal chemistry targeting a surface pocket partly delineated by the L126-Y133 region of PCNA, we identified a potent PCNA inhibitor (AOH1160) and characterized its therapeutic properties and potential toxicity.
resultsAOH1160 selectively kills many types of cancer cells at below micromolar concentrations without causing significant toxicity to a broad range of nonmalignant cells. Mechanistically, AOH1160 interferes with DNA replication, blocks homologous recombination-mediated DNA repair, and causes cell-cycle arrest. It induces apoptosis in cancer cells and sensitizes them to cisplatin treatment. AOH1160 is orally available to animals and suppresses tumor growth in a dosage form compatible to clinical applications. Importantly, it does not cause significant toxicity at 2.5 times of an effective dose.
conclusionsThese results demonstrated the favorable therapeutic properties and the potential of AOH1160 as a broad-spectrum therapeutic agent for cancer treatment.
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