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Abstract
Pyruvate dehydrogenase complex (PDHc) suppression has long been regarded as a mechanism for cancer cells to manifest the well-known Warburg effect. However, in recent years, it has been proposed that whether PDHc is suppressed or activated in cancer development is context-dependent. The PDHc E1 subunit (PDH E1), a thiamine pyrophosphate (TPP)-dependent enzyme, catalyses the first and rate-limiting step of the complex so there is a need for selective PDH E1 inhibitors. Using thiamine/TPP analogues, we have developed potent and selective inhibitors of mammalian PDH E1. These inhibitors will aid work on understanding of the oncogenic role of PDHc and, ultimately, the development of anticancer strategies.
Supplementary materials
Title
Methods and Results
Description
Methods and results for molecular docking, enzyme assays and cell-growth experiments. Synthetic procedures and analytical data for all compounds.
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Title
NMR spectra and references
Description
NMR spectra for key compounds and references
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