ArticleScience advances2019
Targeting dePARylation selectively suppresses DNA repair-defective and PARP inhibitor-resistant malignancies.
Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Parp Inhibitors and Radiotherapy: A New Combination for Prostate Cancer (Systematic Review).International journal of molecular sciences · 2023Pooled it
- Targeting p300 Reverses Acidic Microenvironment-Induced PARP Inhibitor Resistance.Cancer research · 2026Article
- Homogeneous Time-Resolved Fluorescence-Based Assay to Screen ADP-Ribosyl Hydrolase Inhibitors.Bio-protocol · 2026Article
- FET proteins and PARylation-dependent condensates promote replication fork reversal and genome stability.Nature communications · 2026Article
- PARG inhibition in ATM-deficient prostate cancer: from mechanistic discovery to therapeutic potential.Journal of translational medicine · 2026Article
- Targeting MARylation and DePARylation in Cancer Therapy: New Promising Therapeutic Opportunities.Cancers · 2025Review
- Poly (ADP-Ribose) Glycohydrolase-Dependent dePARylation of PCNA Is Essential for DNA Replication.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Identification of parthanatos-related molecular subtypes and development of prognostic risk models in ovarian cancer based on multi-omics analysis.Journal of ovarian research · 2025Article
- Article
- Dual ENPP1/ATM depletion blunts DNA damage repair boosting radioimmune efficacy to abrogate triple-negative breast cancer.Signal transduction and targeted therapy · 2025Article
- DNA polymerase beta expression in head & neck cancer modulates the poly(ADP-ribose)-mediated replication checkpoint.DNA repair · 2025Article
- Clinical approaches to overcome PARP inhibitor resistance.Molecular cancer · 2025Review
- Prospects for PARG inhibitors in cancer therapy.Journal of molecular cell biology · 2025Review
- Angiopoietin-like protein 8 directs DNA damage responses towards apoptosis by stabilizing PARP1-DNA condensates.Cell death and differentiation · 2025Article
- RECQL4 requires PARP1 for recruitment to DNA damage, and PARG dePARylation facilitates its associated role in end joining.Experimental & molecular medicine · 2025Article
- 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
- Poly-ADP-ribosylation dynamics, signaling, and analysis.Environmental and molecular mutagenesis · 2024Review
- ADP-ribose hydrolases: biological functions and potential therapeutic targets.Expert reviews in molecular medicine · 2024Review
- A platform to deliver single and bi-specific Cas9/guide RNA to perturb genes in vitro and in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Low magnesium in conjunction with high homocysteine increases DNA damage in healthy middle aged Australians.European journal of nutrition · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
While poly(ADP-ribosyl)ation (PARylation) plays an important role in DNA repair, the role of dePARylation in DNA repair remains elusive. Here, we report that a novel small molecule identified from the NCI database, COH34, specifically inhibits poly(ADP-ribose) glycohydrolase (PARG), the major dePARylation enzyme, with nanomolar potency in vitro and in vivo. COH34 binds to the catalytic domain of PARG, thereby prolonging PARylation at DNA lesions and trapping DNA repair factors. This compound induces lethality in cancer cells with DNA repair defects and exhibits antitumor activity in xenograft mouse cancer models. Moreover, COH34 can sensitize tumor cells with DNA repair defects to other DNA-damaging agents, such as topoisomerase I inhibitors and DNA-alkylating agents, which are widely used in cancer chemotherapy. Notably, COH34 also efficiently kills PARP inhibitor-resistant cancer cells. Together, our study reveals the molecular mechanism of PARG in DNA repair and provides an effective strategy for future cancer therapies.
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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.