ASP2905

ASP2905, a cell-permeable, potent, selective and orally available KCNH3 inhibitor (IC50 = 9 nM in CHO cells expressing Kv12.2), regulates synthetic RNA riboswitches. Core action includes reversible, high-affinity binding to the AC17-4 RNA aptamer (KD = 7.7 nM), inducing a conformational change activating gene expression (>10-fold, at 5 µM) via ribozyme inhibition or exon skipping. In vivo, oral ASP2905 administration effectively induces reversible hEPO gene expression increase, notably in the liver of mice. Demonstrating low cytotoxicity, ASP2905 and AC17-4 provide a system for precise gene regulation, potentially controlling functional outcomes like myogenic differentiation via MyoD and apoptosis via BAX in HEK-293 cells.