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• W2147895384 abstract "Myotonic dystrophy type 1 (DM1) is caused by an expanded CUG repeat (CUGexp) that sequesters muscleblind-like 1 protein (MBNL1), a protein that regulates alternative splicing. CUGexp RNA is a validated drug target for this currently untreatable disease. Herein, we develop a bioactive small molecule (1) that targets CUGexp RNA and is able to inhibit the CUGexp·MBNL1 interaction in cells that model DM1. The core of this small molecule is based on ligand 2, which was previously reported to be active in an in vitro assay. A polyamine-derivative side chain was conjugated to this core to make it aqueous-soluble and cell-penetrable. In a DM1 cell model this conjugate was found to disperse CUGexp ribonuclear foci, release MBNL1, and partially reverse the mis-splicing of the insulin receptor pre-mRNA. Direct evidence for ribonuclear foci dispersion by this ligand was obtained in a live DM1 cell model using time-lapse confocal microscopy." @default.
• W2147895384 created "2016-06-24" @default.
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• W2147895384 date "2013-03-20" @default.
• W2147895384 modified "2023-10-10" @default.
• W2147895384 title "A Novel CUG^exp·MBNL1 Inhibitor with Therapeutic Potential for Myotonic Dystrophy Type 1" @default.
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• W2147895384 doi "https://doi.org/10.1021/cb400046u" @default.
• W2147895384 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3683132" @default.
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