A chemoinformatics-guided platform for efficient discovery of RNA-binding small molecules: Proof-of-concept for myotonic dystrophy type 1 (opens in new tab)

Structured RNAs cause human diseases but remain challenging to target selectively with small molecules. Here, we report a chemoinformatics-guided discovery framework that integrates fingerprint-based molecular design, experimental validation, and mechanistic profiling to identify small molecules that bind highly structured, disease-associated RNAs. Using an RNA-binder fingerprint derived from known ligands, a Tversky similarity screen of >8 million compounds yielded a 150-member library enric...