N-(1-phenylethyl)-2-(pyrrolidin-1-yl)quinazolin-4-aMine

Description

Importazole is a cell-permeable inhibitor of importin-β, which transports cargo molecules bearing a nuclear localization signal into the nucleus. Importazole prevents nuclear import of GFP-tagged nuclear factor of activated T cells (NFAT-GFP) in HEK293 cells (IC₅₀ = 15 μM), which is reversible upon importazole washout. Importazole does not interfere with transportin-mediated nuclear import or chromosomal maintenance 1 (CRM1)-mediated nuclear export. Importazole inhibits nuclear import of topoisomerase IIβ binding protein 1 (TopBP1) in Xenopus egg extracts and of NF-κB in multiple myeloma cells. It also induces defects in spindle and microtubule formation in vitro.

Uses

Importazole is an importin-β inhibitor.

Uses

Importazole has been used:

• to inhibit importin-β and to elucidate the mechanism of enhanced nuclear localization of heat shock protein 70 (HSP70) by vaccinia-related kinase 3 (VRK3)
• to treat COS?7 cells transfected with the expressing vectors of WT HNF4α , S78A, and S78D to study its effect
• as a KPNB inhibitor to determine whether CREB-regulated co-activator 1 (CRTC1) would be escorted into the nucleus by the classical nuclear localizing sequence (NLS)- dependent machinery
• as a functional inhibitor of Importin β in embryo treatment
• as an?importin?inhibitor to treat the transfected H1299 cells to block nuclear translocation of phosphorylated p53-RS

Definition

ChEBI: N-(1-phenylethyl)-2-(1-pyrrolidinyl)-4-quinazolinamine is a member of quinazolines.

Biochem/physiol Actions

Importazole is an inhibitor of importin-β transport receptors. During interphase, the transport receptor importin-β carries cargoes into the nucleus, where RanGTP releases them. Importazole somehow disrupts the importin/RAN interaction. Importazole is selective among other transporters. Compounds are imported into, but not out of, cells.

References

1) Soderholm et al. (2011), Importazole, a small molecule inhibitor of the transport receptor importin-β; ACS Chem. Biol., 6 700 2) Bird et al. (2013), RanGTP and CLASP1 cooperate to position the mitotic spindle; Mol. Biol. Cell, 24 2506 3) Bai et al. (2014), Importin β-dependent nuclear import of TopBP1 in ATR-Chk1 checkpoint in Xenopus egg extracts; Cell Signal., 26 857 4) Yan et al. (2015), Importin β1 mediates nuclear factor-κB signal transduction into the nuclei of myeloma cells and affects their proliferation and apoptosis; Cell Signal., 27 851 5) Zhu et al. (2018), KPNB1 inhibition disrupts proteostasis and triggers unfolded protein response-mediated apoptosis in glioblastoma cells; Oncogene 37 2936