Abstract
Direct links between altered metabolism, dysregulation of epigenetic processes, and cancer have been established via investigation of cancer- and syndrome-associated mutations in genes encoding key enzymes of intermediary metabolism. Here, we provide an outline for the synthesis of cell-permeable forms of the cellular metabolites (R)-2-hydroxyglutarate and (L)-2-hydroxyglutarate, and their application for the inhibition of α-ketoglutarate-dependent Jumonji histone demethylases.
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Acknowledgments
This work was supported by the W.M. Keck Foundation (A.L.K.), Purdue University Center for Cancer Research (http://www.cancerresearch.purdue.edu) Innovative Pilot and Shared Resource Grants (A.L.K.), and a Bird Stair Fellowship (H.B.). This research was also supported by the National Cancer Institute (http://www.cancer.gov) [CCSG CA23168] for data acquired in the Purdue Computational and Medicinal Chemistry Resource.
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Balduf, H.T., Pepe, A., Kirchmaier, A.L. (2017). Synthesis and Application of Cell-Permeable Metabolites for Modulating Chromatin Modifications Regulated by α-Ketoglutarate-Dependent Enzymes. In: Stefanska, B., MacEwan, D. (eds) Epigenetics and Gene Expression in Cancer, Inflammatory and Immune Diseases. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6743-8_5
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DOI: https://doi.org/10.1007/978-1-4939-6743-8_5
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