Theaflavin binds to a druggable pocket of TMEM16A channel and inhibits lung adenocarcinoma cell viability.

ABSTRACT: As a calcium-activated chloride channel regulated by the intracellular Ca²⁺ concentration and membrane potential, TMEM16A has attracted considerable attention and has been proposed as a novel anticancer drug target. We have previously reported that the pocket above the ion conductance pore could be a nonselective inhibitor-binding pocket. However, whether this pocket is druggable remains unexplored. In this study, we performed virtual screening to target the presumed inhibitor-binding pocket and identified a highly effective TMEM16A inhibitor, theaflavin (TF: a tea polyphenol in black tea). Molecular dynamics simulations revealed that theaflavin adopts a "wedge insertion mode" to block the ion conduction pore and induces pore closure. Moreover, the binding mode showed that the T

SUBMITTER: Shi S 

PROVIDER: S-EPMC8368026 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature