The transport receptor importin-β carries cargoes into the nucleus during interphase. Importazole is a selective Importin-β inhibitor. Importazole at concentration of 50μM specifically binds to importin-β, but not RanQ69L, transportin and CRM1. Importazole at concentration of 100μM could inhibit importin-β NLS (importin-β import substrate)-mediated nuclear import without effect on transportin M9-mediated import. Importazole impaired spindle assembly and disrupted mitotic cargo release and mitotic spindles. Treatment with 12μM Importazole could decrease TNF-α-induced p65 nuclear import and suppressed the expression of NF-κB target gene BCL2, c-IAP1 and XIAP in NCI-H929 and RPMI-8226 cells.
作用机制
Importazole specifically binds to importin-β and alters its interaction with RanGTP.[1]
To investigate the effects of IPZ on meiosis I spindle assembly and function. Results showed that IPZ treatment delayed the resumption of meiosis, reduced the proportion of normal bipolar spindles, and induced spindle disassembly.
EMBO J. 2020 Jan 2;39(1):e101689.
human chondrocytes
40 μM
1 hour
Inhibit Importin β activity and prevent SOX9 from entering the nucleus
Aging Cell. 2016 Jun;15(3):499-508.
HEK 293 cells
40 µM
1 hour
Importazole blocked nuclear import of NFAT-GFP, and this effect was reversible upon drug washout.
ACS Chem Biol. 2011 Jul 15;6(7):700-8.
HeLa cells
100 µM
Importazole blocked nuclear import of the GFP-NLS reporter, causing its enrichment at the nuclear envelope.
ACS Chem Biol. 2011 Jul 15;6(7):700-8.
HeLa cells stably expressing GFP-EB3
40 μM
2 min
To study the effect of Importazole on astral microtubule dynamics. Importazole treatment decreases the number of astral MT/cortex contacts and reduces astral MT elongation speed.
Mol Biol Cell. 2013 Aug;24(16):2506-14.
HeLa cells stably expressing GFP-tubulin and mCherry-H2B
40 μM
60 min
To study the effect of Importazole on spindle dynamics. Importazole treatment causes spindles to move randomly in the cytoplasm, which can be rescued by nocodazole treatment.
Mol Biol Cell. 2013 Aug;24(16):2506-14.
HeLa cells
20 μM or 40 μM
1 h
To study the role of the RanGTP/importin-β pathway in spindle positioning. Importazole treatment results in defects in spindle assembly, chromosome congression, and spindle centering, leading to misoriented spindles. These defects can be partially rescued by importin-β overexpression.
Mol Biol Cell. 2013 Aug;24(16):2506-14.
Xenopus egg extract
2 mM
60 min
Inhibits TopBP1’s nuclear import and MMC-induced Chk1 phosphorylation
Cell Signal. 2014 May;26(5):857-67.
HeLa cells
50 µM
3 h
Blocks importin β1 activity, reducing nuclear translocation of Ank1 and Ank6
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