ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Arylsulfonamide KCN1 inhibits in vivo glioma growth and interferes with HIF signaling by disrupting HIF-1α interaction with cofactors p300/CBP.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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
46 citing papers in PubMed, 78 citations in OpenAlex.
- HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?Acta pharmaceutica Sinica. B · 2026Review
- Preclinical and clinical advances to overcome hypoxia in glioblastoma multiforme.Cell death & disease · 2024Review
- PDK1 promotes breast cancer progression by enhancing the stability and transcriptional activity of HIF-1α.Genes & diseases · 2024Article
- Lactate score classification of hepatocellular carcinoma helps identify patients with tumors that respond to immune checkpoint blockade therapy.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Morphological Observation and Transcriptome Analysis of Ciliogenesis inInternational journal of molecular sciences · 2023Article
- Recurrent Glioblastoma: Ongoing Clinical Challenges and Future Prospects.OncoTargets and therapy · 2023Review
- A systematic study of HIF1A cofactors in hypoxic cancer cells.Scientific reports · 2022Article
- Gene regulation by histone-modifying enzymes under hypoxic conditions: a focus on histone methylation and acetylation.Experimental & molecular medicine · 2022Review
- Article
- Inhibition of the HIF-1 Survival Pathway as a Strategy to Augment Photodynamic Therapy Efficacy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Hypoxia: The Cornerstone of Glioblastoma.International journal of molecular sciences · 2021Review
- Epigenetic and metabolic interplay in cutaneous squamous cell carcinoma.Experimental dermatology · 2021Article
- Novel Benzenesulfonate Scaffolds with a High Anticancer Activity and G2/M Cell Cycle Arrest.Cancers · 2021Article
- Protein Acetylation at the Interface of Genetics, Epigenetics and Environment in Cancer.Metabolites · 2021Review
- Glycometabolic rearrangements--aerobic glycolysis in pancreatic cancer: causes, characteristics and clinical applications.Journal of experimental & clinical cancer research : CR · 2020Review
- The disubstituted adamantyl derivative LW1564 inhibits the growth of cancer cells by targeting mitochondrial respiration and reducing hypoxia-inducible factor (HIF)-1α accumulation.Experimental & molecular medicine · 2020Article
- Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation.Journal of experimental & clinical cancer research : CR · 2020Review
- Stapled Peptides as HIF-1α/p300 Inhibitors: Helicity Enhancement in the Bound State Increases Inhibitory Potency.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Uniaxial Static Strain Promotes Osteoblast Proliferation and Bone Matrix Formation in Distraction Osteogenesis In Vitro.BioMed research international · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
purposeThe hypoxia-inducible factor-1 (HIF-1) plays a critical role in tumor adaptation to hypoxia, and its elevated expression correlates with poor prognosis and treatment failure in patients with cancer. In this study, we determined whether 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, KCN1, the lead inhibitor in a novel class of arylsulfonamide inhibitors of the HIF-1 pathway, had antitumorigenic properties in vivo and further defined its mechanism of action. EXPERIMENTAL
designWe studied the inhibitory effect of systemic KCN1 delivery on the growth of human brain tumors in mice. To define mechanisms of KCN1 anti-HIF activities, we examined its influence on the assembly of a functional HIF-1α/HIF-1β/p300 transcription complex.
resultsKCN1 specifically inhibited HIF reporter gene activity in several glioma cell lines at the nanomolar level. KCN1 also downregulated transcription of endogenous HIF-1 target genes, such as VEGF, Glut-1, and carbonic anhydrase 9, in a hypoxia-responsive element (HRE)-dependent manner. KCN1 potently inhibited the growth of subcutaneous malignant glioma tumor xenografts with minimal adverse effects on the host. It also induced a temporary survival benefit in an intracranial model of glioma but had no effect in a model of melanoma metastasis to the brain. Mechanistically, KCN1 did not downregulate the levels of HIF-1α or other components of the HIF transcriptional complex; rather, it antagonized hypoxia-inducible transcription by disrupting the interaction of HIF-1α with transcriptional coactivators p300/CBP.
conclusionsOur results suggest that the new HIF pathway inhibitor KCN1 has antitumor activity in mouse models, supporting its further translation for the treatment of human tumors displaying hypoxia or HIF overexpression.
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.