Calcium- and voltage-gated potassium (BK) channel activators in the 5β-cholanic acid-3α-ol analogue series with modifications in the lateral chain.

ABSTRACT: Large conductance, calcium- and voltage-gated potassium (BK) channels regulate various physiological processes and represent an attractive target for drug discovery. Numerous BK channel activators are available. However, these agents usually interact with the ubiquitously distributed channel-forming subunit and thus cannot selectively target a particular tissue. We performed a structure-activity relationship study of lithocholic acid (LCA), a cholane that activates BK channels via the accessory BK β1 subunit. The latter protein is highly abundant in smooth muscle but scarce in most other tissues. Modifications to the LCA lateral chain length and functional group yielded two novel smooth muscle BK channel activators in which the substituent at C24 has a small volume and a net negative charg

SUBMITTER: Bukiya AN 

PROVIDER: S-EPMC4193543 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature