ArticleMolecular pharmacology2012
Small-molecule targeting of proliferating cell nuclear antigen chromatin association inhibits tumor cell growth.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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.
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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
54 citing papers in PubMed, 101 citations in OpenAlex.
- Oxymatrine therapy inhibited epidermal cell proliferation and apoptosis in severe plaque psoriasis.The British journal of dermatology · 2019Trial
- Synthesis and Anticancer Evaluation of PCNA Inhibitor AOH1996 Analogs in Cancer Cell Cultures.Molecules (Basel, Switzerland) · 2026Article
- In Silico Analysis of Potential Stabilizer Binding Sites at Protein-RNA Interfaces.Computational and structural biotechnology journal · 2026Article
- AOH1996, an Inhibitor of PCNA, Sensitises Breast Cancer Cells to Cytotoxic Chemotherapy.Breast cancer (Dove Medical Press) · 2026Article
- Histone acetyltransferase 1 promotes ovarian cancer progression by regulating cell proliferation and the cell cycle.Oncology letters · 2025Article
- Targeting PCNA/AR interaction inhibits AR-mediated signaling in castration resistant prostate cancer cells.Oncotarget · 2025Article
- Dihydromyricetin alleviates imiquimod-induced psoriasiform inflammation by inhibiting M1 macrophage polarization.Archives of dermatological research · 2025Article
- Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.Frontiers in pharmacology · 2025Review
- Review
- Identification of a potent PCNA-p15-interaction inhibitor by autodisplay-based peptide library screening.Microbial biotechnology · 2024Article
- The potential of PCNA inhibition as a therapeutic strategy in cervical cancer.Journal of medical virology · 2023Review
- Article
- Molecular Glue Discovery: Current and Future Approaches.Journal of medicinal chemistry · 2023Review
- Proliferating cell nuclear antigen inhibitors block distinct stages of herpes simplex virus infection.PLoS pathogens · 2023Article
- Review
- Review
- Review
- A System for the Evolution of Protein-Protein Interaction Inducers.ACS synthetic biology · 2021Article
- Quantitative immunohistochemistry (IHC) analysis of biomarker combinations for human esophageal squamous cell carcinoma.Annals of translational medicine · 2021Article
- Proliferating cell nuclear antigen directly interacts with androgen receptor and enhances androgen receptor‑mediated signaling.International journal of oncology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Proliferating cell nuclear antigen (PCNA), a potential anticancer target, forms a homotrimer and is required for DNA replication and numerous other cellular processes. The purpose of this study was to identify novel small molecules that modulate PCNA activity to affect tumor cell proliferation. An in silico screen of a compound library against a crystal structure of PCNA and a subsequent structural similarity search of the ZINC chemical database were carried out to derive relevant docking partners. Nine compounds, termed PCNA inhibitors (PCNA-Is), were selected for further characterization. PCNA-I1 selectively bound to PCNA trimers with a dissociation constant (K(d)) of ~0.2 to 0.4 μM. PCNA-Is promoted the formation of SDS-refractory PCNA trimers. PCNA-I1 dose- and time-dependently reduced the chromatin-associated PCNA in cells. Consistent with its effects on PCNA trimer stabilization, PCNA-I1 inhibited the growth of tumor cells of various tissue types with an IC(50) of ~0.2 μM, whereas it affected the growth of nontransformed cells at significantly higher concentrations (IC(50), ~1.6 μM). Moreover, uptake of BrdU was dose-dependently reduced in cells treated with PCNA-I1. Mechanistically the PCNA-Is mimicked the effect of PCNA knockdown by siRNA, inducing cancer cell arrest at both the S and G(2)/M phases. Thus, we have identified a class of compounds that can directly bind to PCNA, stabilize PCNA trimers, reduce PCNA association with chromatin, and inhibit tumor cell growth by inducing a cell cycle arrest. They are valuable tools in studying PCNA function and may be useful for future PCNA-targeted cancer therapy.
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What OpenQuestion holds
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.