ArticleNature communications2019
Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 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
97 citing papers in PubMed, 128 citations in OpenAlex.
- Poly(ADP-ribose) polymerase regulates transient receptor potential channel M2-dependent calpain activation in rd1 mouse retinal degeneration.Neural regeneration research · 2026Article
- Exploiting DNA damage tolerance for precision oncology.Trends in cancer · 2026Review
- JPI-547, a novel dual inhibitor of PARP1/2 and tankyrase is more effective than first-generation PARP inhibitors in preclinical BRCA1/2-mutated cancer models.British journal of cancer · 2026Article
- Decoding PARP roles in breast cancer therapy resistance.Molecular biology reports · 2026Review
- FET proteins and PARylation-dependent condensates promote replication fork reversal and genome stability.Nature communications · 2026Article
- cGAS restricts PARP1-mediated microhomology-mediated end joining by suppressing poly-ADP-ribosylation.Cell death and differentiation · 2026Article
- PARG inhibition in ATM-deficient prostate cancer: from mechanistic discovery to therapeutic potential.Journal of translational medicine · 2026Article
- Role of the ETV5/p38 Signaling Axis in Aggressive Thyroid Cancer Cells.Molecular cancer therapeutics · 2026Article
- Cancer-associated TRF1 mutations alter PARP1 interaction dynamics: an in silico study.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Poly(ADP-ribose) glycohydrolase enforces p21 degradation via dePARylation to promote gastric cancer progression.The Journal of clinical investigation · 2026Article
- Article
- Overcoming Resistance to PARP Inhibitors in BRCA-Mutated Cancers: Mechanisms and Therapeutic Strategies.Journal of Cancer · 2026Review
- DNA damage response inhibitors in pancreatic cancer: progress and challenges.Frontiers in oncology · 2026Review
- Targeting MARylation and DePARylation in Cancer Therapy: New Promising Therapeutic Opportunities.Cancers · 2025Review
- Replication-associated base excision repair/single-strand break repair regulates PARG inhibitor response via the PRMT1/PRMT5/ATR axis.NAR cancer · 2025Article
- The chromatin regulator HELLS mediates SSB repair and responses to DNA alkylation damage.Nucleic acids research · 2025Article
- 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
- Morning clock gene expression in young adults of early and late chronotypes.Scientific reports · 2025Article
- Dual ENPP1/ATM depletion blunts DNA damage repair boosting radioimmune efficacy to abrogate triple-negative breast cancer.Signal transduction and targeted therapy · 2025Article
- Identifying active and inhibitor-resistant MGMT variants for gene therapy.American journal of human genetics · 2025Article
37 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
21 authors at 5 institutions in 2 countries.
Funding
Abstract
Poly(ADP-ribose)ylation (PARylation) by PAR polymerase 1 (PARP1) and PARylation removal by poly(ADP-ribose) glycohydrolase (PARG) critically regulate DNA damage responses; yet, conflicting reports obscure PARG biology and its impact on cancer cell resistance to PARP1 inhibitors. Here, we found that PARG expression is upregulated in many cancers. We employed chemical library screening to identify and optimize methylxanthine derivatives as selective bioavailable PARG inhibitors. Multiple crystal structures reveal how substituent positions on the methylxanthine core dictate binding modes and inducible-complementarity with a PARG-specific tyrosine clasp and arginine switch, supporting inhibitor specificity and a competitive inhibition mechanism. Cell-based assays show selective PARG inhibition and PARP1 hyperPARylation. Moreover, our PARG inhibitor sensitizes cells to radiation-induced DNA damage, suppresses replication fork progression and impedes cancer cell survival. In PARP inhibitor-resistant A172 glioblastoma cells, our PARG inhibitor shows comparable killing to Nedaplatin, providing further proof-of-concept that selectively inhibiting PARG can impair cancer cell survival.
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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.