Myotonic dystrophy: candidate small molecule therapeutics

被引：43

作者：

Konieczny, Piotr ^{[1
,2
,3
]}

Selma-Soriano, Estela ^{[1
,2
,3
]}

Rapisarda, Anna S. ^{[1
,2
,3
]}

Fernandez-Costa, Juan M. ^{[1
,2
,3
]}

Perez-Alonso, Manuel ^{[1
,2
,3
]}

Artero, Ruben ^{[1
,2
,3
]}

机构：

[1] Univ Valencia, Dept Genet & Interdisciplinary Res Struct Biotech, Valencia, Spain

[2] Incliva Hlth Res Inst, Translat Genom Grp, Valencia, Spain

[3] Joint Unit Incliva CIPF, Valencia, Spain

来源：

DRUG DISCOVERY TODAY | 2017年 / 22卷 / 11期

关键词：

CUG TRINUCLEOTIDE REPEATS; DESIGNED SMALL MOLECULES; RNA TOXICITY; DROSOPHILA MODEL; MESSENGER-RNA; MBNL PROTEINS; CELL-LINES; TYPE-1; DM1; IN-VITRO; INHIBITOR;

D O I：

10.1016/j.drudis.2017.07.011

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Myotonic dystrophy type 1 (DM1) is a rare multisystemic neuromuscular disorder caused by expansion of CTG trinucleotide repeats in the noncoding region of the DMPK gene. Mutant DMPK transcripts are toxic and alter gene expression at several levels. Chiefly, the secondary structure formed by CUGs has a strong propensity to capture and retain proteins, like those of the muscleblind-like (MBNL) family. Sequestered MBNL proteins cannot then fulfill their normal functions. Many therapeutic approaches have been explored to reverse these pathological consequences. Here, we review the myriad of small molecules that have been proposed for DM1, including examples obtained from computational rational design, HTS, drug repurposing and therapeutic gene modulation.

引用

页码：1740 / 1748

页数：9

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