ArticleScientific reports2019
Sangivamycin and its derivatives inhibit Haspin-Histone H3-survivin signaling and induce pancreatic cancer cell death.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Kallikrein related peptidases 7 and 10 and their substrate desmoglein 3 are upregulated in early stage pancreatic cancerous lesions.Scientific reports · 2026Article
- Development of 5-hydroxybenzothiophene derivatives as multi-kinase inhibitors with potential anti-cancer activity.Future medicinal chemistry · 2024Article
- Review
- Inhibitory Effect of the HASPIN Inhibitor CHR-6494 on BxPC-3-Luc, A Luciferase-Expressing Pancreatic Cancer Cell Line.Cell journal · 2022Article
- The active kinome: The modern view of how active protein kinase networks fit in biological research.Current opinion in pharmacology · 2022Review
- Sangivamycin is highly effective against SARS-CoV-2 in vitro and has favorable drug properties.JCI insight · 2022Article
- An Outdoor Access Period Improves Chicken Cecal Microbiota and Potentially Increases Micronutrient Biosynthesis.Frontiers in veterinary science · 2022Article
- Cyanobacteria-From the Oceans to the Potential Biotechnological and Biomedical Applications.Marine drugs · 2021Review
- A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures.Viruses · 2020Article
- Design of new disubstituted imidazo[1,2-Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Control of the rubber anthracnose fungus Colletotrichum gloeosporioides using culture filtrate extract from Streptomyces deccanensis QY-3.Antonie van Leeuwenhoek · 2020Article
- Discovery, Synthesis, and Scale-up of Efficient Palladium Catalysts Useful for the Modification of Nucleosides and Heteroarenes.Molecules (Basel, Switzerland) · 2020Review
- Bioinformatic Analysis Reveals GSG2 as a Potential Target for Breast Cancer Therapy.Open life sciences · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Current treatment options for patients with pancreatic cancer are suboptimal, resulting in a five year survival rate of about 9%. Difficulties with treatment are due to an immunosuppressive, fibrotic tumor microenvironment that prevents drugs from reaching tumor cells, but also to the limited efficacy of existing FDA-approved chemotherapeutic compounds. We here show that the nucleoside analog Sangivamycin and its closely-related compound Toyocamycin target PDA cell lines, and are significantly more efficient than Gemcitabine. Using KINOMEscan screening, we identified the kinase Haspin, which is overexpressed in PDA cell lines and human PDA samples, as a main target for both compounds. Inhibition of Haspin leads to a decrease in Histone H3 phosphorylation and prevents Histone H3 binding to survivin, thus providing mechanistic insight of how Sangivamycin targets cell proliferation, mitosis and induces apoptotic cell death. In orthotopically implanted tumors in mice, Sangivamycin was efficient in decreasing the growth of established tumors. In summary, we show that Sangivamycin and derivatives can be an efficient new option for treatment of PDA.
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