ArticleNature communications2017
CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours.
Registry-linked trialOpen access · goldAbstract read
In one paragraph
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02719977 (A Phase I Study of CX5461), which is not on this map. Cited by 340 papers.
0numbers the graph read from it
0cells of the map it votes in
340citing papers in PubMed
19.9field-weighted citation impact, top 1% of its field
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.
A Phase I Study of CX5461
Who cites it
340 citing papers in PubMed, 577 citations in OpenAlex.
- JP-1302 inhibits RNA polymerase I transcription and induces nucleolar stress in cancer cell lines.Cell death discovery · 2026Article
- RAD54L coordinates the nucleolar DNA damage response to maintain rDNA stability.The EMBO journal · 2026Article
- The UVA-induced single-base mutational signature of CX-5461 in human cells.Nucleic acids research · 2026Article
- G-quadruplex DNA reprograms the photochemistry of CX-5461 toward radical-driven anticancer activity.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
- In vivo CRISPR knockout screen identifies Polr1a as a key driver and a potential therapeutic target for melanoma metastasis.Oncogene · 2026Article
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- Detangling knots: the intricate roles of G-quadruplexes in herpesvirus replication.Journal of virology · 2026Review
- G-quadruplex homeostasis is a determinant of PARP inhibitor toxicity in BRCA2-deficient cells.Nature communications · 2026Article
- Recognition of multimolecular G-quadruplex regulates phase separation of cockayne syndrome B.Nucleic acids research · 2026Article
- Structural insights into the binding of CX-5461 and MTR-106 to G-quadruplex DNA.Nucleic acids research · 2026Article
- Genome-wide mapping of DNA G-quadruplexes in Trypanosoma brucei chromatin reveals enrichment in coding regions and transcription start sites.Nucleic acids research · 2026Article
- Sex-linked helicases DDX3X and DDX3Y regulate G-quadruplex-associated stress in neurons.Cell death & disease · 2026Article
- Modulating G-quadruplexes for therapeutic intervention: Structural diversity, stability, and emerging nucleic-acid-based strategies.Molecular therapy. Nucleic acids · 2026Review
- Unveiling the Structural Modifications of Cyanines to Target G‑Quadruplex DNA through Biophysical, Computational, and Transcriptome Analyses.ACS omega · 2026Article
- Collision-induced transfer enhances ligand-binding kinetics in guanine quadruplex DNA.Nucleic acids research · 2026Article
- A small molecule disrupts G4-STAT1 interaction and synergizes with olaparib to drive cancer cell death.Nucleic acids research · 2026Article
- In vivo dynamics of G-quadruplex DNA structures during liver regeneration in mice.Scientific reports · 2026Article
- The SMARCA4 subunit of the SWI/SNF complex prevents genome instability at G quadruplexes.Genome biology · 2026Article
- Rare genetic diseases associated with G-quadruplex-induced replication stress.Communications biology · 2026Review
280 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
39 authors at 7 institutions in 3 countries.
Hong XuDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Marco Di AntonioCancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Steven McKinneyDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.ORCID 0000-0002-1611-0867
Veena MathewTerry Fox Laboratory, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Brandon HoDepartment of Biochemistry and Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, Canada M5S 3E1.
Nigel J O'NeilMichael Smith Laboratories, University of British Columbia, Vancouver, Canada V6T 1Z4.
Nancy Dos SantosAdvanced Therapeutics, BC Cancer Agency and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Jennifer SilvesterCampbell Family Institute for Breast Cancer Research, Princess Margret Cancer Centre, 610 University Avenue, Toronto, Canada M5G 2M9.
Vivien WeiDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Jessica GarciaDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Farhia KabeerDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Daniel LaiDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.ORCID 0000-0001-9203-6323
Priscilla SorianoDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Judit BanáthDepartment of Integrative Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Derek S ChiuDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Damian YapDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.ORCID 0000-0002-5370-4592
Daniel D LeCancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Frank B YeMichael Smith Laboratories, University of British Columbia, Vancouver, Canada V6T 1Z4.
Anni ZhangTerry Fox Laboratory, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Kelsie ThuCampbell Family Institute for Breast Cancer Research, Princess Margret Cancer Centre, 610 University Avenue, Toronto, Canada M5G 2M9.
John SoongSenhwa Biosciences, Inc., 9 F, No.205-1, Section 3, Peihsin Road, Hsintien District, New Taipei City 23143, Taiwan R.O.C.
Shu-Chuan LinSenhwa Biosciences, Inc., 9 F, No.205-1, Section 3, Peihsin Road, Hsintien District, New Taipei City 23143, Taiwan R.O.C.
Angela Hsin Chin TsaiDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Tomo OsakoDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Teresa AlgaraDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Darren N SaundersDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.ORCID 0000-0003-0924-0513
Jason WongDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Jian XianCancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
Marcel B BallyAdvanced Therapeutics, BC Cancer Agency and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
James D BrentonCancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.ORCID 0000-0002-5738-6683
Grant W BrownDepartment of Biochemistry and Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, Canada M5S 3E1.ORCID 0000-0002-9002-5003
Sohrab P ShahDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
David CesconCampbell Family Institute for Breast Cancer Research, Princess Margret Cancer Centre, 610 University Avenue, Toronto, Canada M5G 2M9.
Tak W MakCampbell Family Institute for Breast Cancer Research, Princess Margret Cancer Centre, 610 University Avenue, Toronto, Canada M5G 2M9.
Carlos CaldasCancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
Peter C StirlingTerry Fox Laboratory, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Phil HieterMichael Smith Laboratories, University of British Columbia, Vancouver, Canada V6T 1Z4.
Shankar BalasubramanianCancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Samuel AparicioDepartment of Molecular Oncology, British Columbia Cancer Research Centre, and Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.ORCID 0000-0002-0487-9599
University of British Columbia · CABC Cancer Agency · CAUniversity of Cambridge · GBOntario Institute for Cancer Research · CAHwa Hsia University of Technology · TWUniversity of Toronto · CACancer Research UK · GB
Funding
Cancer Research UK 15601Cancer Research UK 18618Cancer Research UK 19836Cancer Research UK 22905
Abstract
G-quadruplex DNAs form four-stranded helical structures and are proposed to play key roles in different cellular processes. Targeting G-quadruplex DNAs for cancer treatment is a very promising prospect. Here, we show that CX-5461 is a G-quadruplex stabilizer, with specific toxicity against BRCA deficiencies in cancer cells and polyclonal patient-derived xenograft models, including tumours resistant to PARP inhibition. Exposure to CX-5461, and its related drug CX-3543, blocks replication forks and induces ssDNA gaps or breaks. The BRCA and NHEJ pathways are required for the repair of CX-5461 and CX-3543-induced DNA damage and failure to do so leads to lethality. These data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. CX-5461 is now in advanced phase I clinical trial for patients with BRCA1/2 deficient tumours (Canadian trial, NCT02719977, opened May 2016).
Indexed as
G-QuadruplexesAnimalsBase SequenceBenzothiazolesBenzoxazinesBRCA1 ProteinBRCA2 ProteinCaenorhabditis elegansCell Line, TumorChromosomal InstabilityDNA DamageDNA RepairDNA ReplicationDNA, RibosomalFemaleGenome, HumanBenzothiazolesBenzoxazinesBRCA1 ProteinBRCA2 ProteinCX 3543CX 5461DNA, RibosomalNaphthyridinesQuinolones
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
NCT02719977ClinicalTrials.gov
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.