ArticleProceedings of the National Academy of Sciences of the United States of America2002
A synthetic HIV-1 Rev inhibitor interfering with the CRM1-mediated nuclear export.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 127 citations in OpenAlex.
- SFPQ/S100A8 complex induces filaggrin deficiency via selective autophagy and JNK phosphorylation in atopic dermatitis.Cell communication and signaling : CCS · 2026Article
- Preclinical characterization of a reversible XPO1 inhibitor for cancer therapy.Nature communications · 2026Article
- Therapeutic Approaches Interfering with Nuclear Localization Signals: An Emerging Strategy for CNS-Related Diseases.Current neuropharmacology · 2026Review
- SINE compounds activate exportin 1 degradation through an allosteric mechanism.Nature chemical biology · 2025Article
- Review
- Ibetazol, a novel inhibitor of importin β1-mediated nuclear import.Communications biology · 2024Article
- Targeting Viral Transcription for HIV Cure Strategies.Microorganisms · 2024Review
- Novel-and Not So Novel-Inhibitors of the Multifunctional CRM1 Protein.Oncology reviews · 2024Review
- Measurement of HIV Rev-Rev Response Element Functional Activity.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Article
- Inhibition of XPO1 with KPT-330 induces autophagy-dependent apoptosis in gallbladder cancer by activating the p53/mTOR pathway.Journal of translational medicine · 2022Article
- HibeRNAtion: HIV-1 RNA Metabolism and Viral Latency.Frontiers in cellular and infection microbiology · 2022Review
- Inhibition of XPO-1 Mediated Nuclear Export through the Michael-Acceptor Character of Chalcones.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Reversible disruption of XPO1-mediated nuclear export inhibits respiratory syncytial virus (RSV) replication.Scientific reports · 2021Article
- Crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP.Acta crystallographica. Section F, Structural biology communications · 2021Article
- XPO1 inhibitors represent a novel therapeutic option in Adult T-cell Leukemia, triggering p53-mediated caspase-dependent apoptosis.Blood cancer journal · 2021Article
- 10 years into the resurgence of covalent drugs.Future medicinal chemistry · 2021Article
- Filgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation.The Journal of clinical investigation · 2020Article
- XPO1-dependent nuclear export as a target for cancer therapy.Journal of hematology & oncology · 2020Review
- Small Molecule Inhibitors of CRM1.Frontiers in pharmacology · 2020Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The HIV-1 Rev protein is an essential regulator of the HIV-1 mRNA expression that promotes the export of unspliced and partially spliced mRNA. The export receptor for the leucine-rich nuclear export signal (NES) of Rev has recently been recognized as CRM1. We identified a low molecular weight compound PKF050-638 as an inhibitor of HIV-1 Rev. This drug inhibits in a dose-dependent fashion Rev-dependent mRNA expression in a cellular assay for Rev function. We show that PKF050-638 is an inhibitor of the CRM1-mediated Rev nuclear export. By using a quantitative in vitro CRM1-NES cargo-binding assay, we could demonstrate that PKF050-638 disrupts CRM1-NES interaction. This mode of action is confirmed in cell culture because the drug reversibly interferes with the colocalization of CRM1 and Rev in the nucleolus of the cell. In addition, we prove that the inhibition is through direct interaction of the compound with Cys-539 of CRM1. These effects are similar to those of the known CRM1 inhibitor leptomycin B and suggest that the inhibitory effect of the compound is caused by binding to CRM1 at a similar site. The compound displayed strict structural requirements for its activity, as its enantiomer was inactive in all assays tested. These results show that we identified a drug that interferes with the CRM1-mediated nuclear export of Rev through inhibition of the CRM1-NES complex formation. The reversibility of its binding to CRM1 and its availability through chemical synthesis could make it useful for studying CRM1-mediated export pathways.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.