Evidence for effective suppression of INa and IK(DR) by AS2034178 (bis{2-[(4-{(4′-(2-hydroxyethoxy)-2′-methyl[1,1′-biphenyl]-3-yl)methoxy}phenyl]methyl]-3,5-dioxo-1,2,4-oxadiazolidin-4-ide} tetrahydrate), an agonist of free fatty acid receptor

AS2034178, an agonist of free fatty acid receptor-1 or G protein-coupled receptor 40, enhances pancreatic β-cell function. Its impact on ionic currents in excitable cells, particularly pituitary tumor (GH₃) cells, was investigated. AS2034178 suppressed transient (I_Na(T)) and late (I_Na(L)) components of voltage-gated Na⁺ current (I_Na) with IC₅₀ values of 29.8 and 5.3 µM, respectively. It did not alter current–voltage relationship but shifted steady-state inactivation curve of I_Na(T) leftward. AS2034178 also blocked persistent Na⁺ current (I_Na(P)) activated by long-lasting ramp voltages, and subsequent application of deltamethrin or tefluthrin attenuated its suppression. The compound prolonged recovery of I_Na(P) inactivation, shifted its inactivation curve, and shortened time constant for I_N(P) decay. Additionally, AS2034178 suppressed delayed-rectifier K⁺ current (I_K(DR)) with a dissociation constant of 6.23 µM. Docking studies suggested AS2034178′s ability to interact with amino acid residues in hNa_V1.7 channels.(supplementary data). AS2034178′s effects on ionic currents (I_Na and I_K(DR)) contribute to its mechanisms of action in culture or in vivo.