ArticlePloS one2015
Englerin A Agonizes the TRPC4/C5 Cation Channels to Inhibit Tumor Cell Line Proliferation.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
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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.
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Who cites it
67 citing papers in PubMed, 108 citations in OpenAlex.
- Iron and Other Metal Ions in Human Health and Disease.MedComm · 2026Review
- (-)-Englerin A binding to human TRPC5 exposes an aromatic interaction network in channel activation.Nature communications · 2026Article
- Molecular architecture of the human TRPC1/C5 heteromeric channel.Nature communications · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Mechanism of (-)-Englerin A and calcium binding on the human TRPC5 channel.Protein science : a publication of the Protein Society · 2025Article
- Article
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- TRPC5 controls the adrenaline-mediated counter regulation of hypoglycemia.The EMBO journal · 2024Article
- The role of natural products versus miRNA in renal cell carcinoma: implications for disease mechanisms and diagnostic markers.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Functional determinants of lysophospholipid- and voltage-dependent regulation of TRPC5 channel.Cellular and molecular life sciences : CMLS · 2024Article
- Role of TRP channels in carcinogenesis and metastasis: Pathophysiology and regulation by non-coding RNAs.Non-coding RNA research · 2024Review
- Transient Receptor Potential Canonical 5 (TRPC5): Regulation of Heart Rate and Protection against Pathological Cardiac Hypertrophy.Biomolecules · 2024Article
- Targeting Dysregulated Ion Channels in Liver Tumors with Venom Peptides.Molecular cancer therapeutics · 2024Review
- Direct modulation of TRPC ion channels by Gα proteins.Frontiers in physiology · 2024Review
- Plasma Membrane Channel TRPM4 Mediates Immunogenic Therapy-Induced Necrosis.Cancer research · 2023Article
- Expression of pH-Sensitive TRPC4 in Common Skin Tumors.International journal of molecular sciences · 2023Article
- Biological Effects of Modifications of the Englerin A Glycolate.ACS medicinal chemistry letters · 2022Article
- Review
- CaInternational journal of molecular sciences · 2022Review
- An ex vivo perfused ventilated murine lung model suggests lack of acute pulmonary toxicity of the potential novel anticancer agent (-)-englerin A.Archives of toxicology · 2022Article
7 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
32 authors at 4 institutions in 3 countries.
Funding
Abstract
Englerin A is a structurally unique natural product reported to selectively inhibit growth of renal cell carcinoma cell lines. A large scale phenotypic cell profiling experiment (CLiP) of englerin A on ¬over 500 well characterized cancer cell lines showed that englerin A inhibits growth of a subset of tumor cell lines from many lineages, not just renal cell carcinomas. Expression of the TRPC4 cation channel was the cell line feature that best correlated with sensitivity to englerin A, suggesting the hypothesis that TRPC4 is the efficacy target for englerin A. Genetic experiments demonstrate that TRPC4 expression is both necessary and sufficient for englerin A induced growth inhibition. Englerin A induces calcium influx and membrane depolarization in cells expressing high levels of TRPC4 or its close ortholog TRPC5. Electrophysiology experiments confirmed that englerin A is a TRPC4 agonist. Both the englerin A induced current and the englerin A induced growth inhibition can be blocked by the TRPC4/C5 inhibitor ML204. These experiments confirm that activation of TRPC4/C5 channels inhibits tumor cell line proliferation and confirms the TRPC4 target hypothesis generated by the cell line profiling. In selectivity assays englerin A weakly inhibits TRPA1, TRPV3/V4, and TRPM8 which suggests that englerin A may bind a common feature of TRP ion channels. In vivo experiments show that englerin A is lethal in rodents near doses needed to activate the TRPC4 channel. This toxicity suggests that englerin A itself is probably unsuitable for further drug development. However, since englerin A can be synthesized in the laboratory, it may be a useful chemical starting point to identify novel modulators of other TRP family channels.
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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.