WY-46824

WY-46824 potently inhibits human norepinephrine transporter (hNET) binding (K_i = 46 nM) and norepinephrine uptake (IC₅₀ = 58 nM) in MDCK-Net6 cells, shows nearly 300-fold selectivity over human serotonin transporter (hSERT) in JAR cells, but exhibits high affinity for human dopamine transporter (hDAT) (K_i = 53 nM) in CHO cell membranes; the (S)-(−)-enantiomer is the more potent eutomer at hNET (K_i = 14 nM, IC₅₀ = 29 nM) and retains hDAT affinity (K_i = 73 nM)^[1].
WY-46824 (0.001 nM-1 mM) inhibits [³H]nisoxetine binding to hNET in stably transfected HEK-293 whole cells with a K_i of 20 nM, but shows a 275-fold loss of potency (K_i = 5500 nM) in hNET-containing HEK-293 membrane preparations^[2].
WY-46824 (0.001 nM-1 mM; 15 min) inhibits norepinephrine uptake via hNET in stably transfected HEK-293 cells with a K_i of 141 nM^[2].
WY-46824 (5 μM; 30 min-2 h) does not change total or cell surface hNET expression levels in stably hNET-transfected HEK-293 cells^[2].