S3969 fully and reversibly activates hENaC in heterologous cells. S3969 activates δβγ, αβγ, α2βγ, δ2βγ, and αβG37Sγ hENaC with EC50s of 1.2±0.2 μM, 1.2±0.1 μM, 1.2±0.5, 0.4±0.1,and 1.2±0.4 μM[1].
S3969 does not activate αβγ mouse ENaC (mENaC) at concentrations yielding maximal activation of αβγ hENaC or δβγ hENaC. Weak αβγ mENaC activation was observed at high concentrations of S3969 (100-300 μm)[1].
S3969 exhibits high efficacy (600-700% hENaC activation at 30 μm) as well as potency on wild-type hENaC (apparent EC50 ∼1 μm for αβγ hENaC and δβγ hENaC but not αβγ mENaC) [1].
ENaC-activator S3969 (10 µM) stimulates αF61L mutant ENaC more than wild-type ENaC[2].
References:
[1]. Min Lu, et al. Small molecule activator of the human epithelial sodium channel. J Biol Chem. 2008 May 2;283(18):11981-94.
[2]. Regina Huber, et al. Functional characterization of a partial loss-of-function mutation of the epithelial sodium channel (ENaC) associated with atypical cystic fibrosis. Cell Physiol Biochem. 2010;25(1):145-58.