Highly Selective Artificial K+ Channels Reverse Liver Fibrosis In Vivo

Liver fibrosis is a life-threatening disease currently lacking clinically effective therapeutic agents. Given the close correlation between dysregulated intracellular K⁺ homeostasis and the progression of liver fibrosis, developing artificial K⁺ channels mimicking the essential function of their natural counterparts in regulating intracellular K⁺ levels might offer an appealing yet unexplored treatment strategy. Here, we present an unconventional class of artificial K⁺ channels involving the “motional” collaboration between two K⁺ transporter molecules. In particular, <b>6C6 </b>exhibits an impressive EC₅₀ value of 0.28 μM (i.e., 0.28 mol% relative to lipid) towards K⁺ and an exceptionally high K⁺/Na⁺ selectivity of 15.5, representing one of the most selective artificial K⁺ channels reported to date. Most importantly, our study demonstrates, for the first time, the potential therapeutic effect of K⁺-selective artificial ion channels in reversing liver fibrosis both <i>in vitro</i> and <i>in vivo</i>.