PF-06678419

PF-06678419 is a sodium-coupled citrate transporter and sodium-dependent dicarboxylate transporter inhibitor. PF-06678419 inhibits citrate uptake by interacting with residues near and outside NaCT’s citrate binding site. PF-06678419 can be used for the research of type 2 diabetes mellitus^[1][2]. In Vitro:PF-06678419 (Compound 4) (30 min) potently inhibits NaCT-mediated citrate uptake in HEK_NaCT cells with an IC₅₀ of 0.44 μM, but lacks selectivity, also inhibiting NaDC1 and NaDC3 with IC₅₀ values of 5.5 μM and 3.2 μM, respectively^[1].
PF-06678419 binds to the putative citrate binding site of a human NaCT homology model, with key interactions involving residues G228, V231, V232, and G409^[2].
PF-06678419 (10 µM; 12 min) shows altered inhibitory activity against mutant human NaCT-expressing HEK-293 cells, with increased affinity for NaCT^Q77K and NaCT^V231A mutants, reduced activity against NaCT^G228A, NaCT^V232A, NaCT^V232I, NaCT^G409N, and NaCT^R481I mutants, and reduced sensitivity (IC₅₀ ≥25 µM) for NaCT^G228A and NaCT^G409N mutants^[2].