ArticleNucleic acids research2023
Novobiocin blocks nucleic acid binding to Polθ and inhibits stimulation of its ATPase activity.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 29 citations in OpenAlex.
- DNA polymerase theta (Polθ): a novel candidate for targeted cancer therapy.Cancer biology & therapy · 2026Review
- The Pharmacologic Profile of ART6043, a First-in-Class Clinical DNA Polymerase Theta Polymerase Domain Inhibitor Potentiating PARP Inhibitor Efficacy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Exploiting DNA damage tolerance for precision oncology.Trends in cancer · 2026Review
- POLQ promotes tumor progression and immunosuppression via ATM‑P53 signaling in endometrial cancer.Oncology reports · 2026Article
- Coordinated transfer of DNA between Pol θ and Pol δ resets microhomology choice during double-strand break repair.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- State-of-the-Art and Future Directions in Structural Proteomics.Molecular & cellular proteomics : MCP · 2025Review
- Polymerase Ѳ inhibitors combinations with approved and investigational agents in patient-derived tumor multi-cell type (mct) spheroids.Experimental and molecular pathology · 2025Article
- Modulation of Human Colon Cell Activity by Synthetic Coumarin Derivatives Bearing a Phosphonate Group.Molecules (Basel, Switzerland) · 2025Article
- Polymerase theta expression is correlated with proliferative capacity but not with DNA repair deficiency status in solid tumors.NPJ precision oncology · 2025Article
- Examining Instrumental Factors Influencing the Performance of Data-Independent Acquisition Methods in Hydrogen/Deuterium Exchange Mass Spectrometry.Analytical chemistry · 2025Article
- Harnessing transcriptional regulation of alternative end-joining to predict cancer treatment.NAR cancer · 2025Article
- Ligand-receptor interactions combined with histopathology for improved prognostic modeling in HPV-negative head and neck squamous cell carcinoma.NPJ precision oncology · 2025Article
- Cryo-EM Structures of the Plasmodium falciparum Apicoplast DNA Polymerase.Journal of molecular biology · 2024Article
- PARG inhibitor sensitivity correlates with accumulation of single-stranded DNA gaps in preclinical models of ovarian cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Replication stress induces POLQ-mediated structural variant formation throughout common fragile sites after entry into mitosis.Nature communications · 2024Article
- Single-Stranded DNA Gap Accumulation Is a Functional Biomarker for USP1 Inhibitor Sensitivity.Cancer research · 2024Article
- Polθ Inhibitor (ART558) Demonstrates a Synthetic Lethal Effect with PARP and RAD52 Inhibitors in Glioblastoma Cells.International journal of molecular sciences · 2024Article
- Structural basis for a Polθ helicase small-molecule inhibitor revealed by cryo-EM.Nature communications · 2024Article
- Marine-Derived Leads as Anticancer Candidates by Disrupting Hypoxic Signaling through Hypoxia-Inducible Factors Inhibition.Marine drugs · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Polymerase theta (Polθ) acts in DNA replication and repair, and its inhibition is synthetic lethal in BRCA1 and BRCA2-deficient tumor cells. Novobiocin (NVB) is a first-in-class inhibitor of the Polθ ATPase activity, and it is currently being tested in clinical trials as an anti-cancer drug. Here, we investigated the molecular mechanism of NVB-mediated Polθ inhibition. Using hydrogen deuterium exchange-mass spectrometry (HX-MS), biophysical, biochemical, computational and cellular assays, we found NVB is a non-competitive inhibitor of ATP hydrolysis. NVB sugar group deletion resulted in decreased potency and reduced HX-MS interactions, supporting a specific NVB binding orientation. Collective results revealed that NVB binds to an allosteric site to block DNA binding, both in vitro and in cells. Comparisons of The Cancer Genome Atlas (TCGA) tumors and matched controls implied that POLQ upregulation in tumors stems from its role in replication stress responses to increased cell proliferation: this can now be tested in fifteen tumor types by NVB blocking ssDNA-stimulation of ATPase activity, required for Polθ function at replication forks and DNA damage sites. Structural and functional insights provided in this study suggest a path for developing NVB derivatives with improved potency for Polθ inhibition by targeting ssDNA binding with entropically constrained small molecules.
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.