Selective inhibitors of nuclear export (SINEs or SINE compounds) are drugs that block exportin 1 (XPO1 or CRM1), a protein involved in transport from the cell nucleus to the cytoplasm. This causes cell cycle arrest and cell death by apoptosis.[1][2] Thus, SINE compounds are of interest as anticancer drugs; several are in development, and one (selinexor) has been approved for treatment of multiple myeloma as a drug of last resort.
The prototypical nuclear export inhibitor is leptomycin B, a natural product and secondary metabolite of Streptomyces bacteria. Although it is nonselective and too toxic for clinical use in humans, the discovery of its mechanism of action and antitumor properties prompted development of the SINE compounds.[1]
^ abFung HY, Chook YM (2014). "Atomic basis of CRM1-cargo recognition, release and inhibition". Semin Cancer Biol. 27: 52–61. doi:10.1016/j.semcancer.2014.03.002. PMC 4108548. PMID 24631835.
^Gandhi UH, Senapedis W, Baloglu E, Unger TJ, Chari A, Vogl D; et al. (2018). "Clinical implications of targeting XPO1-mediated nuclear export in multiple myeloma". Clin Lymphoma Myeloma Leuk. 18 (5): 335–345. doi:10.1016/j.clml.2018.03.003. PMID 29610030.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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Xpovio among others, is a selectiveinhibitorofnuclearexport used as an anti-cancer medication. It works by blocking the action of exportin 1 and thus blocking...
an immunomodulatory agent selinexor: an orally available selectiveinhibitorofnuclearexport indicated in combination with dexamethasone in people who...
be a potent and specific nuclearexportinhibitor in humans and the fission yeast S. pombe. Leptomycin B alkylates and inhibits CRM1 (chromosomal region...
John (2014). "SINE (selectiveinhibitorofnuclearexport) – translational science in a new class of anti-cancer agents". Journal of Hematology & Oncology...
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phosphorylation of single tyrosine in NFAT mediated by Jnk3 kinase a member of MAPK kinase subfamily. Nuclear import of NFAT and its subsequent export is dependent...
humans is encoded by the NR4A1 gene. Nuclear receptor 4A1 (NR4A1) is a member of the NR4A nuclear receptor family of intracellular transcription factors...
domestic and export purposes. France operated a small plant during the 1950s and 1960s.[citation needed] Deuterium oxide is used in nuclear magnetic resonance...
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Specifically, PD1 inhibits the binding of viral RNA to specific nuclearexport factors in the host cells, thus blocking the exportof viral RNA from the...
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number of death receptor ligands (such as TNF or TRAIL), antagonize the anti-apoptotic Bcl-2 pathway, or introduce Smac mimetics to inhibit the inhibitor (IAPs)...
genetic dosage of the main TGF-beta ligand of the embryo, Nodal. Further supporting a role as TGF-beta inhibitor, tissue-selective deletion of ectodermin...
assortments of enzymes responsible for selectively modifying protein cargo. These modifications influence the fate of the protein. The compartmentalization of the...
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