ArticleJournal of chemical biology2015
Design and activity of AP endonuclease-1 inhibitors.
Article in Journal of chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Miniaturization and characterization of patient derived hepatocellular carcinoma tumor organoid cultures for cancer drug discovery applications.SLAS discovery : advancing life sciences R & D · 2025Article
- Targeting APE1: Advancements in the Diagnosis and Treatment of Tumors.Protein and peptide letters · 2025Review
- Identification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease.Nature communications · 2024Article
- AP endonuclease 1: Biological updates and advances in activity analysis.Methods in enzymology · 2024Article
- Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons.Cells · 2023Review
- Characterizing inhibitors of human AP endonuclease 1.PloS one · 2023Article
- Unbiased High-Throughput Drug Combination Pilot Screening Identifies Synergistic Drug Combinations Effective against Patient-Derived and Drug-Resistant Melanoma Cell Lines.SLAS discovery : advancing life sciences R & D · 2021Article
- Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer.Cell death & disease · 2021Article
- The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease.Drug discovery today · 2021Review
- Insight intoACS omega · 2020Article
- PD-1-Targeted Discovery of Peptide Inhibitors by Virtual Screening, Molecular Dynamics Simulation, and Surface Plasmon Resonance.Molecules (Basel, Switzerland) · 2019Article
- Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma Cells.Molecules (Basel, Switzerland) · 2019Article
- Structural insight into the serotonin (5-HT) receptor family by molecular docking, molecular dynamics simulation and systems pharmacology analysis.Acta pharmacologica Sinica · 2019Article
- Computational Systems Pharmacology-Target Mapping for Fentanyl-Laced Cocaine Overdose.ACS chemical neuroscience · 2019Article
- Insight of Captagon Abuse by Chemogenomics Knowledgebase-guided Systems Pharmacology Target Mapping Analyses.Scientific reports · 2019Article
- APE1: A skilled nucleic acid surgeon.DNA repair · 2018Review
- An insight into paracetamol and its metabolites using molecular docking and molecular dynamics simulation.Journal of molecular modeling · 2018Article
- A novel class of chemicals that react with abasic sites in DNA and specifically kill B cell cancers.PloS one · 2017Article
- Metal binding mediated conformational change of XPA protein:a potential cytotoxic mechanism of nickel in the nucleotide excision repair.Journal of molecular modeling · 2016Article
- Difference and Influence of Inactive and Active States of Cannabinoid Receptor Subtype CB2: From Conformation to Drug Discovery.Journal of chemical information and modeling · 2016Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Apurinic/apyrimidinic endonuclease-1/redox effector factor-1 (APE-1) is a critical component of base excision repair that excises abasic lesions created enzymatically by the action of DNA glycosylases on modified bases and non-enzymatically by hydrolytic depurination/depyrimidination of nucleobases. Many anticancer drugs generate DNA adducts that are processed by base excision repair, and tumor resistance is frequently associated with enhanced APE-1 expression. Accordingly, APE-1 is a potential therapeutic target to treat cancer. Using computational approaches and the high resolution structure of APE-1, we developed a 5-point pharmacophore model for APE-1 small molecule inhibitors. One of the nM APE-1 inhibitors (AJAY-4) that was identified based on this model exhibited an overall median growth inhibition (GI50) of 4.19 μM in the NCI-60 cell line panel. The mechanism of action is shown to be related to the buildup of abasic sites that cause PARP activation and PARP cleavage, and the activation of caspase-3 and caspase-7, which is consistent with cell death by apoptosis. In a drug combination growth inhibition screen conducted in 10 randomly selected NCI-60 cell lines and with 20 clinically used non-genotoxic anticancer drugs, a synergy was flagged in the SK-MEL-5 melanoma cell line exposed to combinations of vemurafenib, which targets melanoma cells with V600E mutated BRAF, and AJAY-4, our most potent APE-1 inhibitor. The synergy between AJAY-4 and vemurafenib was not observed in cell lines expressing wild-type B-Raf protein. This synergistic combination may provide a solution to the resistance that develops in tumors treated with B-Raf-targeting drugs.
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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.