Disease Relevance
Some studies have shown that cells that lack insulin (or are insensitive to insulin) overexpress PDK4. As a result, the pyruvate formed from glycolysis cannot be oxidized which leads to hyperglycaemia due to the fact that glucose in the blood cannot be used efficiently. Therefore several drugs target PDK4 hoping to treat type II diabetes.
PDK1 has shown to have increased activity in hypoxic cancer cells due to the presence of HIF-1. PDK1 shunts pyruvate away from the citric acid cycle and keeps the hypoxic cell alive. Therefore, PDK1 inhibition has been suggested as an antitumor therapy since PDK1 prevents apoptosis in these cancerous cells. Similarly, PDK3 has been shown to be overexpressed in colon cancer cell lines. Three proposed inhibitors are AZD7545 and Dichloroacetate which both bind to PDK1, and Radicicol which binds to PDK3.
Read more about this topic: Pyruvate Dehydrogenase Kinase
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