ArticleACS chemical biology2017
Identification of Small Molecule Translesion Synthesis Inhibitors That Target the Rev1-CT/RIR Protein-Protein Interaction.
Article in ACS chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 55 citations in OpenAlex.
- Docking-Based Virtual Screening Identifies a Small-Molecule Inhibitor of the Translesion Synthesis REV7/REV3 Protein-Protein Interaction.ChemMedChem · 2026Article
- Sensitization of cancer cells to DNA-damaging agents by expression of the REV1 C-terminal domain: Implications for chemotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Human TLS DNA polymerase: saviors or threats under replication stress?Molecular and cellular biochemistry · 2025Review
- Protein Assemblies in Translesion Synthesis.Genes · 2024Review
- Lead compound profiling for small molecule inhibitors of the REV1-CT/RIR Translesion synthesis Protein-Protein interaction.Bioorganic & medicinal chemistry · 2024Article
- Human CST complex restricts excessive PrimPol repriming upon UV induced replication stress by suppressing p21.Nucleic acids research · 2024Article
- Cellular resistance mechanisms in cancer and the new approaches to overcome resistance mechanisms chemotherapy.Saudi medical journal · 2023Article
- REV7 in Cancer Biology and Management.Cancers · 2023Review
- Exploiting replication gaps for cancer therapy.Molecular cell · 2022Review
- REV1: A novel biomarker and potential therapeutic target for various cancers.Frontiers in genetics · 2022Article
- REV1 Inhibition Enhances Radioresistance and Autophagy.Cancers · 2021Article
- Protein-Protein Interactions in Translesion Synthesis.Molecules (Basel, Switzerland) · 2021Review
- Targeting protein-protein interactions in the DNA damage response pathways for cancer chemotherapy.RSC chemical biology · 2021Review
- Structure-Based Drug Design of Phenazopyridine Derivatives as Inhibitors of Rev1 Interactions in Translesion Synthesis.ChemMedChem · 2021Article
- Disruption of DNA polymerase ζ engages an innate immune response.Cell reports · 2021Article
- DNA Damage Tolerance Pathways in Human Cells: A Potential Therapeutic Target.Frontiers in oncology · 2021Review
- Targeting translesion synthesis (TLS) to expose replication gaps, a unique cancer vulnerability.Expert opinion on therapeutic targets · 2021Review
- Translesion synthesis inhibitors as a new class of cancer chemotherapeutics.Expert opinion on investigational drugs · 2021Review
- Antitumor Drugs and Their Targets.Molecules (Basel, Switzerland) · 2020Review
- REV1 inhibitor JH-RE-06 enhances tumor cell response to chemotherapy by triggering senescence hallmarks.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Translesion synthesis (TLS) is an important mechanism through which proliferating cells tolerate DNA damage during replication. The mutagenic Rev1/Polζ-dependent branch of TLS helps cancer cells survive first-line genotoxic chemotherapy and introduces mutations that can contribute to the acquired resistance so often observed with standard anticancer regimens. As such, inhibition of Rev1/Polζ-dependent TLS has recently emerged as a strategy to enhance the efficacy of first-line chemotherapy and reduce the acquisition of chemoresistance by decreasing tumor mutation rate. The TLS DNA polymerase Rev1 serves as an integral scaffolding protein that mediates the assembly of the active multiprotein TLS complexes. Protein-protein interactions (PPIs) between the C-terminal domain of Rev1 (Rev1-CT) and the Rev1-interacting region (RIR) of other TLS DNA polymerases play an essential role in regulating TLS activity. To probe whether disrupting the Rev1-CT/RIR PPI is a valid approach for developing a new class of targeted anticancer agents, we designed a fluorescence polarization-based assay that was utilized in a pilot screen for small molecule inhibitors of this PPI. Two small molecule scaffolds that disrupt this interaction were identified, and secondary validation assays confirmed that compound 5 binds to Rev1-CT at the RIR interface. Finally, survival and mutagenesis assays in mouse embryonic fibroblasts and human fibrosarcoma HT1080 cells treated with cisplatin and ultraviolet light indicate that these compounds inhibit mutagenic Rev1/Polζ-dependent TLS in cells, validating the Rev1-CT/RIR PPI for future anticancer drug discovery and identifying the first small molecule inhibitors of TLS that target Rev1-CT.
Indexed as
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.