(2--(4-aminophenyl)-(2-5--bi-1h-benzimidazol)-5-amine) and Myotonic-Dystrophy

RNA is an important drug target, but current approaches to identify bioactive small molecules have been engineered primarily for protein targets. Moreover, the identification of small molecules that bind a specific RNA target with sufficient potency remains a challenge. Computer-aided drug design (CADD) and, in particular, ligand-based drug design provide a myriad of tools to identify rapidly new chemical entities for modulating a target based on previous knowledge of active compounds without relying on a ligand complex. Herein we describe pharmacophore virtual screening based on previously reported active molecules that target the toxic RNA that causes myotonic dystrophy type 1 (DM1). DM1-associated defects are caused by sequestration of muscleblind-like 1 protein (MBNL1), an alternative splicing regulator, by expanded CUG repeats (r(CUG)

Topics: Alternative Splicing; Animals; Computer-Aided Design; DNA-Binding Proteins; Drug Design; Humans; Mice; Molecular Targeted Therapy; Myotonic Dystrophy; RNA; RNA-Binding Proteins; Small Molecule Libraries