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BA6b9 is an allosteric inhibitor of SK4 channels that targets the CaM–PIP2-binding domain with a IC50 value of 8.6 μM (WT SK4). BA6b9 inhibits SK4 channels by interacting with two specific residues, Arg191 and His192 in the S4–S5 linker. BA6b9 significantly prolongs atrial and atrioventricular effective refractory period (ERP) and reduces atrial fibrillation (AF) induction in rat isolated hearts, which has the potential to be used for the research of arrhythmia [1]. | [References]
[1] Shira Burg, et al. Allosteric inhibitors targeting the calmodulin-PIP2 interface of SK4 K+ channels for atrial fibrillation treatment. Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2202926119. |
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