ArticleScience advances2016
Syrosingopine sensitizes cancer cells to killing by metformin.
Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 79 citations in OpenAlex.
- Lactate-induced epithelial-mesenchymal transition: a metabolic nexus in pancreatic cancer metastasis.Translational cancer research · 2026Review
- Repurposing Syrosingopine for Cancer Therapy: Lactate Trapping and ISR Sensitization as Metabolic Vulnerabilities.Oncology and therapy · 2026Review
- Lactate metabolic reprogramming and lactylation modification: molecular mechanisms reshaping the tumor immunosuppressive microenvironment.Cell & bioscience · 2026Review
- Protein Lactylation in Liver Disease: A Comprehensive Review.Expert reviews in molecular medicine · 2026Review
- Metformin and its derivatives in breast cancer: from glycaemic control to tumor-intrinsic pathways.Breast cancer research : BCR · 2025Review
- Tumor-stromal metabolic crosstalk in pancreatic cancer.Trends in cell biology · 2025Review
- Itaconate transport across the plasma membrane and Salmonella-containing vacuole via MCT1/4 modulates macrophage antibacterial activity.Nature communications · 2025Article
- Review
- Burning lactic acid: a road to revitalizing antitumor immunity.Frontiers of medicine · 2025Review
- Repurposing brucine as a chemopreventive agent in mammary gland carcinoma: Regulating lactate transport through MCT-4.Toxicology reports · 2025Article
- Metformin sensitizes triple-negative breast cancer to histone deacetylase inhibitors by targeting FGFR4.Journal of biomedical science · 2025Article
- Lactate metabolism in clonal plasma cells and its therapeutic implications in multiple myeloma patients with elevated serum LDH levels.Cancer & metabolism · 2025Article
- Optimized Nanostructured Lipid Carriers for Metformin: Enhanced Anti-Inflammatory Activity and Protection Against Type 2 Diabetes-Induced Organ Damage.International journal of nanomedicine · 2025Article
- Lactate-induced lactylation: from basic research to clinical perspectives.Frontiers in pharmacology · 2025Review
- Fueling CARs: metabolic strategies to enhance CAR T-cell therapy.Experimental hematology & oncology · 2024Review
- Syrosingopine, an anti-hypertensive drug and lactate transporter (MCT1/4) inhibitor, activates hepatic stellate cells and exacerbates liver fibrosis in a mouse model.Genes & diseases · 2024Article
- Syrosingopine and UK5099 synergistically suppress non-small cell lung cancer by activating the integrated stress response.Cell death & disease · 2024Article
- Alternatively activated macrophages are associated with faster growth rate in vestibular schwannoma.Brain communications · 2024Article
- Exploring monocarboxylate transporter inhibition for cancer treatment.Exploration of targeted anti-tumor therapy · 2024Review
- Lactylation: The emerging frontier in post-translational modification.Frontiers in genetics · 2024Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report that the anticancer activity of the widely used diabetic drug metformin is strongly potentiated by syrosingopine. Synthetic lethality elicited by combining the two drugs is synergistic and specific to transformed cells. This effect is unrelated to syrosingopine's known role as an inhibitor of the vesicular monoamine transporters. Syrosingopine binds to the glycolytic enzyme α-enolase in vitro, and the expression of the γ-enolase isoform correlates with nonresponsiveness to the drug combination. Syrosingopine sensitized cancer cells to metformin and its more potent derivative phenformin far below the individual toxic threshold of each compound. Thus, combining syrosingopine and codrugs is a promising therapeutic strategy for clinical application for the treatment of cancer.
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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.