PDK4-IN-1 hydrochloride

PDK4-IN-1 hydrochloride is an anthraquinone derivative and a potent and orally active inhibitor of pyruvate dehydrogenase kinase 4 (PDK4, IC50 value = 84 nM) . (In Vitro) :PDK4-IN-1 hydrochloride 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 hydrochloride. In HCT116 and RKO cells, PDK4-IN-1 hydrochloride) treatment dose-dependently increased apoptosis. PDK4-IN-1 hydrochloride decreases the expression of BCL-xL and increases the expression of BAX. Cleavage of PARP1 and caspase 3 are increased by PDK4-IN-1 hydrochloride. (In Vivo) :PDK4-IN-1 hydrochlorideimproved glucose tolerance in diet-induced obese mice and ameliorated allergic reactions in a passive cutaneous anaphylaxis mouse model. PDK4-IN-1 hydrochloride (C57BL/6J mice) treatment significantly improves glucose tolerance. Pre-incubation with PDK4-IN-1 (compound 8c) dose-dependently inhibits the release of β-hexosaminidase from IgE/antigen-activated BMMCs.