THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS
发明人:
ZIMMERMAN, STEVEN C.,LUU, LONG M.,NGUYEN, LEIN T.T.
申请号：
CA2956464
公开号：
CA2956464A1
申请日:
2015.08.10
申请国别(地区):
CA
年份:
2016
代理人:
摘要：
The invention provides compounds, compositions and therapeutic methods. The compounds and compositions can be used for the treatment of myotonic dystrophy. The compounds can selectively bind to CUG repeats in RNA, or to CTG repeats in DNA, and inhibit replication of the nucleic acids. RNA-targeted therapeutic agents for the treatment of myotonic dystrophy type 1 (DM1) are described. In one embodiment, two bisamidinium ligands are linked using "click" chemistry to form a heterodimer that is a potent inhibitor of the MBNL1 -rCUGexp complex (K I = 25 ± 8 nM), is relatively non-toxic to HeLa cells, dissolves nuclear foci, corrects >；80% of the IR misregulated alternative splicing in DM1 model cells (1 µ?), and shows improvement of disease phenotypes in a DM1 Drosophila model.
