Chemical Name: N-[4-(2-Chloro-5-methyl-4-pyrimidinyl)phenyl]-N-[[4-[[(2,2-difluoroacetyl)amino]methyl]phenyl]methyl]-2,4-dihydroxybenzamide
Biological ActivityVER 246608 is a potent and ATP-competitive inhibitor of pyruvate dehydrogenase kinase (PDK; IC50s = 35, 40, 84, and 91 nM for PDK-1, PDK-3, PDK-2, and PDK-4 respectively). It is selective for PDKs over a panel of 97 kinases and HSP90. VER 246608 increases pyruvate dehydrogenase complex activity, oxygen consumption and reduces glycolytic activity; it reduces the production of L-lactate in PC3 cells in D-glucose and L-glutamine depleted media. In PC3 cells, VER 246608 induces cell cycle arrest at the G1 phase under glucose or serum-depleted conditions characteristic of the tumor microenvironment.
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