S3969 is a small molecule activator of the human epithelial sodium channel (ENaC) with EC50 of 1.2 uM in ENaC-expressing oocytes. S3969 can fully and reversibly activates human ENaC (hENaC) in an amiloride-sensitive and dose-dependent manner in heterologous cells. S3969 activates hENaC following removal of amiloride, increases hENaC open probability. S3969 activates δβγ hENaC but not αβγ mENaC, opens ENaC channels not cleaved by furin proteolysis. S3969 increases hENaC open probability through interactions requiring the extracellular domain of the β subunit.
