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Description

A cell-permeable diaminoquinazoline compound that selectively blocks importin-beta-mediated nuclear import of NLS- (nuclear localization signal) bearing cargos (IC50 = 15 µ,M against Ca+2-induced NFAT nuclear import in HEK293 cells) in a reversible manner without affecting transportin-dependent nuclear import of M9 signal-containing cargos or CRM1-mediated nuclear export., A cell-permeable diaminoquinazoline compound that selectively blocks importin-beta-mediated nuclear import of NLS- (nuclear localization signal) bearing cargos (IC50 = 15 µ,M against Ca+2-induced NFAT nuclear import in HEK293 cells) in a reversible manner without affecting transportin-dependent nuclear import of M9 signal-containing cargos or CRM1-mediated nuclear export. IPZ affects, but not blocks, importin-beta-RanGTP interaction, likely by inducing a conformational change upon direct importin-beta binding. IPZ treatment impairs cellular mitosis and is cytotoxic to HeLa cells (50% and >90% killing in 24 h, respectively, with 22.5 and 60 µ,M IPZ).