IC50: 84 nM (Pyruvate dehydrogenase kinase 4 (PDK4))

PDK4-IN-1 (Compound 8c; 50 μM; 0-72 hours; HCT116 and RKO cells) 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.
PDK4-IN-1 (Compound 8c; 10-50 μM; 24 hours; HCT116 and RKO cells) treatment dose-dependently increased apoptosis.
PDK4-IN-1 (Compound 8c; 10 μM; 24 hours; HEK293T cells) treatment inhibits phosphorylation of Ser ²³² , Ser ²⁹³ , and Ser ³⁰⁰ of PDHE1α.
10 μM of PDK4-IN-1 (Compound 8c) significantly increases p-Akt in AML12 cells.
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.

PDK4-IN-1 (Compound 8c; 100 mg/kg; oral administration; daily; for 1 week; 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, 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.
The pharmacokinetic (PK) profiles of PDK4-IN-1 (compound 8c) are evaluated in rat. PDK4-IN-1 shows good bioavailability (64%), long half-life (>7 h), and moderate clearance (CL of 0.69) in rats.