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Plant metabolites from natural product extracts offer unique advantages against carcinogenesis in the development of drugs. The target-based virtual screening from food-derived compounds represents a promising approach for tumor therapy. In this study, we performed virtual screening to target the presumed inhibitor-binding pocket and identified a highly potent Kv10.1 inhibitor, liensinine (Lien), which can inhibit the channel in a dose-dependent way with an IC50 of 0.24 ± 0.07 μM. Combining molecular dynamics simulations with mutagenesis experiments, our data show that Lien interacts with Kv10.1 by binding with Y539, T543, D551, E553, and H601 in the C-linker domain of Kv10.1. In addition, the interaction of sequence alignment and 3D structural modeling revealed differences between the C-linker domain of the Kv10.1 channel and the Kv11.1 channel. Furthermore, antitumor experiments revealed that Lien suppresses the proliferation and migration of HCC both in vitro and in vivo. In summary, the food-derived compound, Lien, may serve as a lead compound for antihepatoma therapeutic drugs targeting Kv10.1.
Ma et al. (Wed,) studied this question.