Biological Activity
JX06 is a potent, PDK1-selective, covalent pyruvate dehydrogenase (PDH) kinase (PDHK, PDK) inhibitor (PDK1/2/3 IC50 = 49/101/313 nM; PDK4 IC50 >10 μM, IC50 >10 μM against >300 other kinases). JX06 inhibits cellular PDK substrate PDHA1 Ser293/232 phosphorylation, resulting in reduced aerobic glycolysis and cancer proliferation in cultures (1-10 μM) and in mice in vivo (40-80 mg/kg via daily i.p. injection; A549 & HT-29 xenografts). JX06 is shown to target PDK1 Cys240 for covalent modification.
