ArticleOncotarget2016
Identification of small molecule inhibitors of ERCC1-XPF that inhibit DNA repair and potentiate cisplatin efficacy in cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- XPF mediates 3' flap processing for FEN1-independent Okazaki fragment maturation.Nucleic acids research · 2026Article
- Natural bioactive molecules and chemotherapeutics synergism for enhanced cancer therapy.Nutrition & metabolism · 2026Review
- XPF mediates 3' flap processing for FEN1-independent Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2025Article
- Article
- Unveiling Novel ERCC1-XPF Complex Inhibitors: Bridging the Gap from In Silico Exploration to Experimental Design.International journal of molecular sciences · 2024Article
- ERCC4: a potential regulatory factor in inflammatory bowel disease and inflammation-associated colorectal cancer.Frontiers in endocrinology · 2024Review
- Base Excision Repair: Mechanisms and Impact in Biology, Disease, and Medicine.International journal of molecular sciences · 2023Review
- ATR inhibition overcomes platinum tolerance associated with ERCC1- and p53-deficiency by inducing replication catastrophe.NAR cancer · 2023Article
- Identifying novel biomarkers associated with bladder cancer treatment outcomes.Frontiers in oncology · 2023Review
- Review
- Article
- Article
- Association between ERCC1 Gene Polymorphism (rs11615) and Colorectal Cancer Susceptibility: A Meta-Analysis of Medical Image Fusion and Safety Applications.Computational and mathematical methods in medicine · 2022Article
- Recent Advances in the Development of Non-PIKKs Targeting Small Molecule Inhibitors of DNA Double-Strand Break Repair.Frontiers in oncology · 2022Review
- Modulation of ERCC1-XPF Heterodimerization InhibitionFrontiers in oncology · 2022Article
- MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage.Nucleic acids research · 2021Article
- Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment.International journal of molecular sciences · 2021Review
- Enhancing the activity of platinum-based drugs by improved inhibitors of ERCC1-XPF-mediated DNA repair.Cancer chemotherapy and pharmacology · 2021Article
- Role of Nucleotide Excision Repair in Cisplatin Resistance.International journal of molecular sciences · 2020Review
- Clinical Perspectives of ERCC1 in Bladder Cancer.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
ERCC1-XPF heterodimer is a 5'-3' structure-specific endonuclease which is essential in multiple DNA repair pathways in mammalian cells. ERCC1-XPF (ERCC1-ERCC4) repairs cisplatin-DNA intrastrand adducts and interstrand crosslinks and its specific inhibition has been shown to enhance cisplatin cytotoxicity in cancer cells. In this study, we describe a high throughput screen (HTS) used to identify small molecules that inhibit the endonuclease activity of ERCC1-XPF. Primary screens identified two compounds that inhibit ERCC1-XPF activity in the nanomolar range. These compounds were validated in secondary screens against two other non-related endonucleases to ensure specificity. Results from these screens were validated using an in vitro gel-based nuclease assay. Electrophoretic mobility shift assays (EMSAs) further show that these compounds do not inhibit the binding of purified ERCC1-XPF to DNA. Next, in lung cancer cells these compounds potentiated cisplatin cytotoxicity and inhibited DNA repair. Structure activity relationship (SAR) studies identified related compounds for one of the original Hits, which also potentiated cisplatin cytotoxicity in cancer cells. Excitingly, dosing with NSC16168 compound potentiated cisplatin antitumor activity in a lung cancer xenograft model. Further development of ERCC1-XPF DNA repair inhibitors is expected to sensitize cancer cells to DNA damage-based chemotherapy.
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Identifiers
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.