The trypanosomal pyruvate carrier is found to be rather insensitive to inhibition by alpha-cyano-4-hydroxycinnamate (K i =17 mM) but can be completely blocked by UK-5099 (K i =49 microM). UK-5099 also inhibits the monocarboxylate transporter (MCT) . UK5099 significantly inhibits the glucose-stimulated rise in oxygen consumption in a dose-dependent manner and at 150 μM reduced oxygen consumption below basal levels. UK5099 reduces ATP levels and increases ADP and AMP levels in 832/13 cells. The UK5099 treated cells show significantly higher proportion of side population fraction and express higher levels of stemness markers Oct3/4 and Nanog. UK5099 application may be an ideal model for Warburg effect studies.
The MPC inhibitor UK5099 increases the glucose excursion seen during an intraperitoneal glucose tolerance test in C57BLK mice.