An aminobenzimidazole derivative that selectively and reversibly blocks small conductance Ca2+-activated K+ channels (SK1-3; =420nM, 600nM, and 730nM for SK1, SK2, SK3, respectively) in a Ca2+-dependent manner. It mediates channel gating by interacting with gating structures deep within the inner pore vestibule where Ser507 and Ala532 are deemed to be important for inhibition. Interacts at a site that is distinct from the apamin binding site in SK channels. Can access high-affinity binding sites from both the inside and outside of the cell membrane. Does not affect QT intervals, but prolongs the atrial effective refractive period and prevents acetylcholine-induced atrial fibrillations in ex vivo and in vivo models. Also shown to reversibly block TRPM7 channel (IC50=1.6mM) in smooth muscle cells, primary podocytes, HEK293 cells expressing TRPM7, and ventricular myocytes in a Mg2+-dependent manner and blocks the motility of cells in culture.
Method for Determining Identity:Proton NMR Spectroscopic and Mass Spectrometric analysis
Storage and Stability:Lyophilized and reconstituted products are stable for 6 months after receipt at -20°C. Hygroscopic. Keep tightly closed and desiccated under inert atmosphere. Light sensitive. For maximum recovery of product, centrifuge the original vial prior to removing the cap.
