ArticleCommunications biology2024
Ibetazol, a novel inhibitor of importin β1-mediated nuclear import.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Nucleoporins in Cancer: Functional Roles and Therapeutic Opportunities.Cancer discovery · 2026Article
- Preclinical characterization of a reversible XPO1 inhibitor for cancer therapy.Nature communications · 2026Article
- Cytoplasmic mRNA decay by the antiviral nuclease RNase L promotes transcriptional repression.Cell reports · 2026Article
- Inhibition of nuclear import suppresses androgen receptor action and overcomes resistance in prostate cancer.BMC cancer · 2026Article
- Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.Oncology research · 2026Review
- SINE compounds activate exportin 1 degradation through an allosteric mechanism.Nature chemical biology · 2025Article
- The nuclear import receptor importin-7 targets HPV from the Golgi to the nucleus to promote infection.Science advances · 2025Article
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleocytoplasmatic transport plays an essential role in eukaryotic cell homeostasis and is mediated by karyopherins. Importin β1 (KPNB1) and its adaptor protein importin α1 (KPNA2) are the best-characterized karyopherins that effect nuclear import. Here, we identify a novel small-molecule inhibitor of the importin β1-mediated nuclear import. We design a reporter cell line by stably tagging endogenous importin α1 with a fluorescent protein to screen for compounds affecting its subcellular localization. We identify a series of compounds that trigger cytoplasmatic accumulation of importin α1. The lead compound, ibetazol, is further characterized in a broad sequence of cellular nuclear transport assays. Ibetazol is shown to inhibit all importin β1-mediated nuclear import quickly and specifically, without affecting transport mediated by other karyopherins. Detailed molecular mechanism of action studies demonstrate that ibetazol inhibits importin β1 by covalently targeting Cys585. In summary, ibetazol is a novel small molecule inhibitor of importin β1 enabling pharmacological inhibition of the importin β1-mediated nuclear import process with wide applicability in different fields.
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