PF-06649298 is an inhibitor of sodium-coupled citrate transporter which specifically interacts with NaCT with an IC 50 value of 16.2 μM to inhibits the transport of citrate in human hepatocytes. PF-06649298 can be used in regulating metabolism of glucose and metabolism of lipid [1] [2].

PF-06649298, at concentrations ranging from 0 to 100 μM over a 30-minute incubation period, demonstrates selective inhibition of citrate uptake, particularly targeting the NaCT transporter over dicarboxylate transporters NaDC1 and NaDC3. This effect is observed across HEK-293 cells (expressing NaCT, NaDC1, or NaDC3), human hepatocytes, and mouse hepatocytes, with IC50 values of 408 nM, >100 μM, >100 μM, 16.2 μM, and 4.5 μM, respectively. These findings underscore the compound's specific action on citrate transport mechanisms within the tested cell types.

PF-06649298 (250 mg/kg; p.o. twice a day; for 21 days) effectively mitigates glucose intolerance in high-fat diet (HFD) mice [1], significantly reducing plasma glucose, hepatic triglycerides, diacylglycerides, and acyl-carnitines levels, thus reversing glucose intolerance in HFD-induced mice [2].