ArticleMolecular cancer therapeutics2021
Repurposing the Antidepressant Sertraline as SHMT Inhibitor to Suppress Serine/Glycine Synthesis-Addicted Breast Tumor Growth.
Article in Molecular cancer therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 79 citations in OpenAlex.
- Article
- Normoxic HIFα-mediated metabolic rewiring in cancer as a novel therapeutic target of tumor heterogeneity.Cancer & metabolism · 2026Article
- Review
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- Targeting the noncanonical function of metabolic enzyme PHGDH in driving PD-L1 expression and cancer immune evasion.Cell reports. Medicine · 2026Article
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- Proteomics in Antitumor Drug Target Discovery, Toxicity, Resistance, and Precision Oncology.Drug design, development and therapy · 2026Review
- Article
- Dynamic Metabolic States in TNBC: Orchestrating Spatiotemporal Adaptation and Therapy.Oncology research · 2026Review
- Clioquinol as a new therapy in epilepsy: From preclinical evidence to a proof-of-concept clinical study.Epilepsia · 2025Article
- Repurposing the Antidepressant Sertraline: A Systematic Scoping Review of Its Anticancer Mechanisms.Pharmacology research & perspectives · 2025Article
- Drug repurposing in oncology: a path beyond the bottleneck.Medical oncology (Northwood, London, England) · 2025Review
- Machine Learning Model for Predicting Sertraline-like Activities and Its Impact on Cancer Chemosensitization.ACS chemical neuroscience · 2025Article
- One-Carbon Metabolism Inhibition Depletes Purines and Results in Profound and Prolonged Ewing Sarcoma Growth Suppression.Cancer research communications · 2025Article
- Amino acid metabolism in breast cancer: pathogenic drivers and therapeutic opportunities.Protein & cell · 2025Review
- Metabolic Adaptations in Cancer Progression: Optimization Strategies and Therapeutic Targets.Cancers · 2025Review
- Inhibition Of One-Carbon Metabolism In Ewing Sarcoma Results In Profound And Prolonged Growth Suppression Associated With Purine Depletion.bioRxiv : the preprint server for biology · 2025Article
- Ribosome specialization by cancer-associated ribosomal protein mutations: progress made and open questions.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- The role and research progress of serine metabolism in tumor cells.Frontiers in oncology · 2025Review
- Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer.Clinical Medicine Insights. Oncology · 2025Review
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
Metabolic rewiring is a hallmark of cancer that supports tumor growth, survival, and chemotherapy resistance. Although normal cells often rely on extracellular serine and glycine supply, a significant subset of cancers becomes addicted to intracellular serine/glycine synthesis, offering an attractive drug target. Previously developed inhibitors of serine/glycine synthesis enzymes did not reach clinical trials due to unfavorable pharmacokinetic profiles, implying that further efforts to identify clinically applicable drugs targeting this pathway are required. In this study, we aimed to develop therapies that can rapidly enter the clinical practice by focusing on drug repurposing, as their safety and cost-effectiveness have been optimized before. Using a yeast model system, we repurposed two compounds, sertraline and thimerosal, for their selective toxicity against serine/glycine synthesis-addicted breast cancer and T-cell acute lymphoblastic leukemia cell lines. Isotope tracer metabolomics, computational docking, enzymatic assays, and drug-target interaction studies revealed that sertraline and thimerosal inhibit serine/glycine synthesis enzymes serine hydroxymethyltransferase and phosphoglycerate dehydrogenase, respectively. In addition, we demonstrated that sertraline's antiproliferative activity was further aggravated by mitochondrial inhibitors, such as the antimalarial artemether, by causing G
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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.