Myotonic dystrophy: candidate small molecule therapeutics.
Drug Discov Today
; 22(11): 1740-1748, 2017 11.
Article
in En
| MEDLINE
| ID: mdl-28780071
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Design
/
Myotonin-Protein Kinase
/
Myotonic Dystrophy
Limits:
Animals
/
Humans
Language:
En
Journal:
Drug Discov Today
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2017
Document type:
Article
Affiliation country:
España
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM