ArticleJournal of medicinal chemistry2013
Discovery of a potent inhibitor of replication protein a protein-protein interactions using a fragment-linking approach.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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.
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
31 citing papers in PubMed, 67 citations in OpenAlex.
- RPA hyperphosphorylation hinders the resolution of R-loops and G-quadruplex-associated R-loops during RAS-driven senescence.Nucleic acids research · 2026Article
- Targeting DNA damage sensors for cancer therapy.DNA repair · 2025Review
- Drugging Challenging Cancer Targets Using Fragment-Based Methods.Chemical reviews · 2025Review
- Perspectives on Applications ofMolecules (Basel, Switzerland) · 2024Review
- Structure-Based Drug Design with a Deep Hierarchical Generative Model.Journal of chemical information and modeling · 2024Article
- Identification of small-molecule binding sites of a ubiquitin-conjugating enzyme-UBE2T through fragment-based screening.Protein science : a publication of the Protein Society · 2024Article
- Review
- Identification of a small-molecule inhibitor that selectively blocks DNA-binding by Trypanosoma brucei replication protein A1.Nature communications · 2023Article
- CSAlign and CSAlign-Dock: Structure alignment of ligands considering full flexibility and application to protein-ligand docking.Computational and structural biotechnology journal · 2023Article
- Recent Advancement in Drug Design and Discovery of Pyrazole Biomolecules as Cancer and Inflammation Therapeutics.Molecules (Basel, Switzerland) · 2022Review
- A fragment-based approach to discovery of Receptor for Advanced Glycation End products inhibitors.Proteins · 2021Article
- Applications of Solution NMR in Drug Discovery.Molecules (Basel, Switzerland) · 2021Review
- Article
- Determinants of replication protein A subunit interactions revealed using a phosphomimetic peptide.The Journal of biological chemistry · 2020Article
- Structure-Guided Optimization of Replication Protein A (RPA)-DNA Interaction Inhibitors.ACS medicinal chemistry letters · 2020Article
- Application of Fragment-Based Drug Discovery to Versatile Targets.Frontiers in molecular biosciences · 2020Review
- Repurposing DNA repair factors to eradicate tumor cells upon radiotherapy.Translational cancer research · 2017Article
- Interactive Roles of DNA Helicases and Translocases with the Single-Stranded DNA Binding Protein RPA in Nucleic Acid Metabolism.International journal of molecular sciences · 2017Review
- Recent advancements in the discovery of protein-protein interaction inhibitors of replication protein A.MedChemComm · 2017Review
- DARC: Mapping Surface Topography by Ray-Casting for Effective Virtual Screening at Protein Interaction Sites.Journal of medicinal chemistry · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Replication protein A (RPA), the major eukaryotic single-stranded DNA (ssDNA)-binding protein, is involved in nearly all cellular DNA transactions. The RPA N-terminal domain (RPA70N) is a recruitment site for proteins involved in DNA-damage response and repair. Selective inhibition of these protein-protein interactions has the potential to inhibit the DNA-damage response and to sensitize cancer cells to DNA-damaging agents without affecting other functions of RPA. To discover a potent, selective inhibitor of the RPA70N protein-protein interactions to test this hypothesis, we used NMR spectroscopy to identify fragment hits that bind to two adjacent sites in the basic cleft of RPA70N. High-resolution X-ray crystal structures of RPA70N-ligand complexes revealed how these fragments bind to RPA and guided the design of linked compounds that simultaneously occupy both sites. We have synthesized linked molecules that bind to RPA70N with submicromolar affinity and minimal disruption of RPA's interaction with ssDNA.
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.