PF-06761281 has been used as a SLC13A family inhibitor, in rats to determine its unbound partition coefficient (Kpuu), to estimate its potency as a drug.
PF-06761281 is a small, polar dicarboxylate compound. Its structure is similar to citrate, which is the endogenous substrate of Na+-citrate cotransporter (NaCT). It is a novel, potent inhibitor of SLC13a2/3/5 (solute channel) family, along with selectivity for NaCT.
PF-06761281 is an inhibitor of the sodium-coupled citrate transporter (NaCT or SLC13A5), which may be a target for tretment and prevention of metabolic disorders. The SLC13 transporters SLC13A2 (NaDC1), SLC13A3 (NaDC3), and SLC13A5 (NaCT) co-transport di- and tricarboxylates with multiple sodium ions into cells. PF-06761281 inhibits citrate uptake with an IC50 of 740 nM for NaCT in human hepatocytes. PF-06761281 has >25-fold in vitro selectivity for NaCT over NaDC1 and NaDC3 and was inactive in a selectivity panel of 65 targets.
