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.

1型强直性肌营养不良症（DM1）是一种罕见的多系统性神经肌肉疾病，由DMPK基因非编码区中CTG三核苷酸重复序列的扩增引起。突变的DMPK转录物具有毒性，并在几个水平上改变基因表达。首先，由CUG形成的二级结构具有很强的捕获和保留蛋白质的倾向，就像肌盲样（MBNL）家族的蛋白质一样。螯合的MBNL蛋白然后不能履行其正常功能。已经探索了许多治疗方法来扭转这些病理后果。在这里，我们回顾了已为DM1提出的无数小分子，包括从计算合理设计，HTS，药物再利用和治疗性基因调节中获得的实例。