ArticleJournal of molecular medicine (Berlin, Germany)2015
NNC 55-0396, a T-type Ca2+ channel inhibitor, inhibits angiogenesis via suppression of hypoxia-inducible factor-1α signal transduction.
Article in Journal of molecular medicine (Berlin, Germany), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Systematic review of the osteogenic effect of rare earth nanomaterials and the underlying mechanisms.Journal of nanobiotechnology · 2024Pooled it
- Iron and Other Metal Ions in Human Health and Disease.MedComm · 2026Review
- <p>Regulatory networks of HIFs in tumor‑infiltrating immune cells: From molecular mechanisms to therapeutic implications (Review)</p>.International journal of oncology · 2026Review
- NFATc3 Enhances DREAM Complex-Driven Transactivation.bioRxiv : the preprint server for biology · 2026Article
- Modulators of epithelial-mesenchymal transitions in prostate cancer: potential for novel therapeutics development.Frontiers in pharmacology · 2026Article
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Blockade of CaBritish journal of pharmacology · 2024Article
- Tetralol derivative NNC-55-0396 targets hypoxic cells in the glioblastoma microenvironment: an organ-on-chip approach.Cell death & disease · 2024Article
- Associations between HIFs and tumor immune checkpoints: mechanism and therapy.Discover oncology · 2024Review
- Proton-sensing ion channels, GPCRs and calcium signaling regulated by them: implications for cancer.Frontiers in cell and developmental biology · 2024Review
- Characterization of the TRPV6 calcium channel-specific phenotype by RNA-seq in castration-resistant human prostate cancer cells.Frontiers in genetics · 2023Article
- T-Type Calcium Channels: A Mixed Blessing.International journal of molecular sciences · 2022Review
- Glioblastoma: Current Status, Emerging Targets, and Recent Advances.Journal of medicinal chemistry · 2022Review
- Physiological Overview of the Potential Link between the UPS and CaAntioxidants (Basel, Switzerland) · 2022Review
- Calcium and calcium-related proteins in endometrial cancer: opportunities for pharmacological intervention.International journal of biological sciences · 2022Review
- Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target.International journal of molecular sciences · 2021Review
- Piezo type mechanosensitive ion channel component 1 facilitates gastric cancer omentum metastasis.Journal of cellular and molecular medicine · 2021Article
- Ways into Understanding HIF Inhibition.Cancers · 2021Review
- A comprehensive review in improving delivery of small-molecule chemotherapeutic agents overcoming the blood-brain/brain tumor barriers for glioblastoma treatment.Drug delivery · 2019Review
- The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy.Expert opinion on drug discovery · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledMitochondrial respiration is required for hypoxia-inducible factor (HIF)-1α stabilization, which is important for tumor cell survival, proliferation, and angiogenesis. Herein, small molecules that inhibit HIF-1α protein stability by targeting mitochondrial energy production were screened using the Library of Pharmacologically Active Compounds and cell growth assay in galactose or glucose medium. NNC 55-0396, a T-type Ca(2+) channel inhibitor, was selected as a hit from among 1,280 small molecules. NNC 55-0396 suppressed mitochondrial reactive oxygen species-mediated HIF-1α expression as well as stabilization by inhibiting protein synthesis in a dose-dependent manner. NNC 55-0396 inhibited tumor-induced angiogenesis in vitro and in vivo by suppressing HIF-1α stability. Moreover, NNC 55-0396 significantly suppressed glioblastoma tumor growth in a xenograft model. Thus, NNC 55-0396, a small molecule targeting T-type Ca(2+) channel, was identified by the systemic cell-based assay and was shown to have antiangiogenic activity via the suppression of HIF-1α signal transduction. These results provide new insights into the biological network between ion channel and HIF-1α signal transduction. KEY MESSAGE: HIF-1α overexpression has been demonstrated in hypoxic cancer cells. NNC 55-0396, a T-type Ca(2+) channel inhibitor, inhibited HIF-1α expression via both proteasomal degradation and protein synthesis pathways. T-type Ca(2+) channel inhibitors block angiogenesis by suppressing HIF-1α stability and synthesis. NNC 55-0396 could be a potential therapeutic drug candidate for cancer treatment.
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Registered trials
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