Selective inhibitors of nuclear export
WebJun 19, 2024 · Kinetoplastids, including Trypanosoma brucei, control gene expression primarily at the posttranscriptional level.Nuclear mRNA export is an important, but … WebMar 1, 2013 · LMB, a selective inhibitor of Crm1 and exportin 1, disrupts the ternary complex, causing nuclear accumulation of proteins with a functional NES motif. ... Further, they observed an inhibition of nuclear export for expanded Htt. Although we did not find a polyglutamine-dependent effect on the NES function of N17 as they did, our results are ...
Selective inhibitors of nuclear export
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WebAug 8, 2016 · XPO1 is the primary nuclear exporter of key tumor suppressor and growth regulatory proteins, including p53, p73, p21, p27, NPM1, FOXO, and I-ĸβ. 5, 6 Because the majority of these proteins require nuclear localization for their genome-surveying activities, increased nuclear export leads to decreased activity. 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. 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.
WebJul 1, 2024 · Selinexor, a selective inhibitor of nuclear export, has shown activity in haematological malignancies and solid tumours. Selinexor targets XPO1 (exportin 1), increases apoptosis in cancer cells, and modulates the cytoplasmatic levels of messenger-RNA transcripts for c-Myc, Bcl-2, and Bcl-6. In the SADAL trial, subgroup analyses suggest … WebNov 30, 2016 · Author Summary Our data demonstrate that novel selective inhibitor of nuclear export (SINE) compounds reduced viral replication of three related New World alphaviruses, VEEV, EEEV, and WEEV, indicating that CRM1 is instrumental to their life cycle. The novel CRM1 inhibitors have a large selective index and represent a potential pan …
WebDec 17, 2024 · Selinexor is a novel first-in-class oral selective inhibitor of nuclear export, that has meaningful activity in heavily pre-treated r/r DLBCL and other hematological and … WebJul 1, 2024 · Selinexor, a selective inhibitor of nuclear export, has shown activity in haematological malignancies and solid tumours. Selinexor targets XPO1 (exportin 1), …
WebOct 21, 2024 · New 2,3-disubstituted thieno[2,3-d]pyrimidin-4(3H)-ones were synthesized via a one-pot reaction from 2H-thieno[2,3-d] [1,3]oxazine-2,4(1H)-diones, aromatic aldehydes, and benzylamine or 4-hydroxylbezylamine. The obtained compounds were tested in vitro for cancer cell growth inhibition. Compound 19 can inhibit all four types of tested cancer …
WebOrally bioavailable selective inhibitors of nuclear export (SINE) that irreversibly bind to and inhibit the function of XPO1 have been recently developed. The aim of this study was to … small grocery ad templateWebNuclear export inhibitors are of keen interest because they can inhibit several active tumorigenic processes simultaneously and also synergize with other targeted drugs and … song tend to my flowersWebJan 29, 2024 · Nuclear export inhibitors are of keen interest because they can inhibit several active tumorigenic processes simultaneously and also synergize with other targeted drugs and chemotherapy. small grocery chains in canadaWebJun 15, 2015 · Citation 27 Our data show that CRM1 inhibition can induce nuclear retention of Foxo1. A Recent study reported that cytoplasmic localization inactivated the negative cell cycle regulator p27 in colorectal cancer. Citation 8 Our results show that S109 increases the expression of p27 and blocks its nuclear export. Given the key roles of CRM1 in ... small grk trim head screwsWebselective inhibitors of nuclear export (SINE) that irreversibly bind to and inhibit the function of XPO1 have been recently developed. The aim of this study was to investigate the efficacy of the clinical staged, orally available, SINE compound, KPT … song tennessee flat top box johnny cashWebOct 15, 2014 · Exportins belong to the karyopherin β superfamily. Exportin-1 (XPO1), also known as chromosomal region maintenance 1 (CRM1), mediates transport of around 220 … small grocery carts usedWebNov 29, 2012 · Small molecule selective inhibitors of nuclear export (SINEs) were designed that specifically inhibit XPO1. Genetic experiments and X-ray structures demonstrate that SINE covalently bind to a cysteine residue in the cargo-binding groove of XPO1, thereby inhibiting nuclear export of cargo proteins. small grocery in napa