ArticleScientific reports2019
Anti-alcohol abuse drug disulfiram inhibits human PHGDH via disruption of its active tetrameric form through a specific cysteine oxidation.
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 33 papers.
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Who cites it
33 citing papers in PubMed, 60 citations in OpenAlex.
- PHGDH in cancer: a narrative review of its functions beyond serine metabolism.Translational cancer research · 2026Review
- Repurposing Disulfiram for Cancer Therapy: Mechanistic Insights and Translational Challenges.International journal of molecular sciences · 2026Review
- Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence.iScience · 2026Article
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- Clioquinol as a new therapy in epilepsy: From preclinical evidence to a proof-of-concept clinical study.Epilepsia · 2025Article
- Protein post-translational modifications in serine synthetic pathway: functions and molecular mechanisms.Cell communication and signaling : CCS · 2025Review
- Vitamin A Metabolism and Resistance of Hepatic Metastases to Immunotherapy.Molecular cancer therapeutics · 2025Review
- Recent progress in serine metabolism reprogramming in tumors and strategies for serine deprivation.Frontiers in oncology · 2025Review
- Imaging phenotype reveals that disulfirams induce protein insolubility in the mitochondrial matrix.Scientific reports · 2024Article
- Disulfiram and cancer immunotherapy: Advanced nano-delivery systems and potential therapeutic strategies.International journal of pharmaceutics: X · 2024Review
- Cycling back to folate metabolism in cancer.Nature cancer · 2024Review
- Advancing Cancer Therapy with Copper/Disulfiram Nanomedicines and Drug Delivery Systems.Pharmaceutics · 2023Review
- Article
- Virtual Screening of FDA-Approved Drugs for Enhanced Binding with Mitochondrial Aldehyde Dehydrogenase.Molecules (Basel, Switzerland) · 2022Article
- Inhibition of Phosphoglycerate Dehydrogenase Radiosensitizes Human Colorectal Cancer Cells under Hypoxic Conditions.Cancers · 2022Article
- Discovery of Triple Inhibitors of Both SARS-CoV-2 Proteases and Human Cathepsin L.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Computational Investigation of Structural Basis for Enhanced Binding of Isoflavone Analogues with Mitochondrial Aldehyde Dehydrogenase.ACS omega · 2022Article
- Disulfiram in glioma: Literature review of drug repurposing.Frontiers in pharmacology · 2022Review
- Identification of a novel PHGDH covalent inhibitor by chemical proteomics and phenotypic profiling.Acta pharmaceutica Sinica. B · 2022Article
- Biophysical and biochemical properties of PHGDH revealed by studies on PHGDH inhibitors.Cellular and molecular life sciences : CMLS · 2021Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Due to rising costs and the difficulty to identify new targets, drug repurposing appears as a viable strategy for the development of new anti-cancer treatments. Although the interest of disulfiram (DSF), an anti-alcohol drug, to treat cancer was reported for many years, it is only very recently that one anticancer mechanism-of-action was highlighted. This would involve the inhibition of the p97 segregase adaptor NPL4, which is essential for the turnover of proteins involved in multiple regulatory and stress-response intracellular pathways. However, recently DSF was also reported as one of the first phosphoglycerate dehydrogenase (PHGDH) inhibitors, a tetrameric enzyme catalyzing the initial step of the serine synthetic pathway that is highly expressed in numerous cancer types. Here, we investigated the structure-activity relationships (SAR) of PHGDH inhibition by disulfiram analogues as well as the mechanism of action of DSF on PHGDH via enzymatic and cell-based evaluation, mass spectrometric and mutagenesis experiments.
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