PRX-2904

PRX-2904 (compound 31) (0.001-30 μM) inhibits KNa1.1 currents in HEK-TREX cells stably expressing human KNa1.1-WT with an IC₅₀ of 40 nM; the IC₅₀ values for mouse KNa1.1-WT and KNa1.1-P905L are 622 nM and 1012 nM, respectively^[1].
PRX-2904 inhibits multiple human KCNT1 GoF variants, with IC₅₀ values ranging from 221-1768 nM, among which the IC₅₀ values for G288S and F346L are 221 nM and 1768 nM, respectively^[1].
In a binding displacement screen against 80 potential secondary targets, PRX-2904 (10 μM) shows >50% activity only at TSPO and the GABA_A Cl⁻ channel, with displacement rates of 63% and 74%, respectively; meanwhile, its IC₅₀ values for hERG, hNaV1.5, CaV1.2, I_Ks, BK, and KNa1.2 are 11.9, 42, 10.7, 18.5, 13.2, and 16.4 μM, respectively, supporting its good selectivity for KNa1.1^[1].
PRX-2904 (1, 10 μM) does not reduce action potential firing at 1 μM, whereas 10 μM decreases the total number of action potentials from 284.4 to 223.4 in CA1 pyramidal neurons of acute brain slices from P16-30 Kcnt1^L/L mice; in WT mouse brain slices, neither 1 μM nor 10 μM markedly alters total action potential firing^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.