PDK4-IN-1, an anthraquinone derivative, is a potent and orally active inhibitor of pyruvate dehydrogenase kinase 4 (PDK4) with an IC50 value of 84 nM.

PDK4:84 nM

PDK4-IN-1 treatment significantly impedes the proliferation of human colon cancer cell lines, HCT116 and RKO. The colony formation efficiency in HCT116 and RKO cells Is significantly reduced after treatment of PDK4-IN-1[1]. PDK4-IN-1 (Compound 8c; 10-50 μM; 24 hours; HCT116 and RKO cells) treatment dose-dependently increased apoptosis. PDK4-IN-1 (compound 8c)-induced phosphorylation of p53 on serine 15 is a dose-dependent response in both HCT116 and RKO cells. PDK4-IN-1 decreases the expression of BCL-xL and increases the expression of BAX. Cleavage of PARP1 and caspase 3 are increased by PDK4-IN-1[1].

PDK4-IN-1 treatment significantly improves glucose tolerance. Pre-incubation with PDK4-IN-1 dose-dependently inhibits the release of β-hexosaminidase from IgE/antigen-activated BMMCs, showing that the absorbance values are 0.26, 0.20, and 0.126 in IgE/Ag, 10 μM, and 20 μM PDK4-IN-1-treated BMMCs[1].