ArticleScientific reports2021
Ubiquitin-mediated DNA damage response is synthetic lethal with G-quadruplex stabilizer CX-5461.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 21 citations in OpenAlex.
- The UVA-induced single-base mutational signature of CX-5461 in human cells.Nucleic acids research · 2026Article
- G-quadruplex structures as regulators of cellular processes and drivers of genome instability in cancer.Critical reviews in biochemistry and molecular biology · 2026Review
- Structural insights into the binding of CX-5461 and MTR-106 to G-quadruplex DNA.Nucleic acids research · 2026Article
- Emerging roles of POLR2L of RNA polymerase II dynamics and disease mechanisms (Review).Molecular medicine reports · 2026Review
- EpCAM-PSMA: Potential predictors of treatment outcomes for PSMA-targeted alpha therapies in metastatic castration-resistant prostate cancer.Molecular therapy. Oncology · 2026Article
- G-quadruplex stabilization via small molecules as a potential anti-cancer strategy.Cellular & molecular biology letters · 2026Review
- Ubiquitin System-Driven Proteostasis in DNA Damage Response.International journal of molecular sciences · 2026Review
- ATRX loss couples genome instability at a G-rich repeat to dysregulation of human alpha-globin expression.Nature communications · 2026Article
- Natural G-Quadruplex Stabilizers: A Targeted Strategy for Breast Cancer Therapy.Drug design, development and therapy · 2026Review
- Stabilization of G-Quadruplexes Modulates the Expression of DNA Damage and Unfolded Protein Response Genes in Canine Lymphoma/Leukemia Cells.International journal of molecular sciences · 2025Article
- ARID1A stabilizes non-homologous end joining factors at DNA breaks induced by the G4 ligand pyridostatin.Cell reports · 2025Article
- Review
- The G-quadruplex ligand CX-5461: an innovative candidate for disease treatment.Journal of translational medicine · 2025Review
- Structural mechanisms of SLF1 interactions with Histone H4 and RAD18 at the stalled replication fork.Nucleic acids research · 2024Article
- Microhomology-Mediated End-Joining Chronicles: Tracing the Evolutionary Footprints of Genome Protection.Annual review of cell and developmental biology · 2024Review
- Emerging Roles of RNF168 in Tumor Progression.Molecules (Basel, Switzerland) · 2023Review
- Crosstalk between G-quadruplex and ROS.Cell death & disease · 2023Review
- Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy.Nature communications · 2022Article
- Results of the phase I CCTG IND.231 trial of CX-5461 in patients with advanced solid tumors enriched for DNA-repair deficiencies.Nature communications · 2022Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
CX-5461 is a G-quadruplex (G4) ligand currently in trials with initial indications of clinical activity in cancers with defects in homologous recombination repair. To identify more genetic defects that could sensitize tumors to CX-5461, we tested synthetic lethality for 480 DNA repair and genome maintenance genes to CX-5461, pyridostatin (PDS), a structurally unrelated G4-specific stabilizer, and BMH-21, which binds GC-rich DNA but not G4 structures. We identified multiple members of HRD, Fanconi Anemia pathways, and POLQ, a polymerase with a helicase domain important for G4 structure resolution. Significant synthetic lethality was observed with UBE2N and RNF168, key members of the DNA damage response associated ubiquitin signaling pathway. Loss-of-function of RNF168 and UBE2N resulted in significantly lower cell survival in the presence of CX-5461 and PDS but not BMH-21. RNF168 recruitment and histone ubiquitination increased with CX-5461 treatment, and nuclear ubiquitination response frequently co-localized with G4 structures. Pharmacological inhibition of UBE2N acted synergistically with CX-5461. In conclusion, we have uncovered novel genetic vulnerabilities to CX-5461 with potential significance for patient selection in future clinical trials.
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.