Creatine kinases (CKs) have emerged as a metabolic liability in many rapidly proliferating cancers. We have developed a class of covalent inhibitors that impair creatine phosphagen energetics by targeting a redox-regulated cysteine residue in the active site of CKs.
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References
Fenouille, N. et al. The creatine kinase pathway is a metabolic vulnerability in EVI1-positive acute myeloid leukemia. Nat. Med. 23, 301–313 (2017). An article describing CK as a vulnearbility in AML.
Loo, J. M. et al. Extracellular metabolic energetics can promote cancer progression. Cell 160, 393–406 (2015). This article describes creatine energetics as a vulnerability in liver metastases.
Maguire, O. A. et al. Creatine-mediated crosstalk between adipocytes and cancer cells regulates obesity-driven breast cancer. Cell Metab. 33, 499–512 (2021). An article describing creatine energetics as a vulnerability in breast cancers.
Xiao, H. et al. A quantitative tissue-specific landscape of protein redox regulation during aging. Cell 180, 968–983 (2020). This article describes the redox sensitivity of CK isoforms in vivo.
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This is a summary of: Darabedian, N. et al. Depletion of creatine phosphagen energetics with a covalent creatine kinase inhibitor. Nat. Chem. Bio. https://doi.org/10.1038/s41589-023-01273-x (2023).
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A creatine kinase inhibitor targeting a redox-regulated cysteine. Nat Chem Biol (2023). https://doi.org/10.1038/s41589-023-01274-w
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DOI: https://doi.org/10.1038/s41589-023-01274-w
