Targeting RNA structures with small molecules

[kntkb]

https://www.nature.com/articles/s41573-022-00521-4

Excellent summary of small molecules to target RNA. Discusses about hit finding to assay methods with many illustrations. Table 1-3 summaries small molecules binding to different kinds of RNA and Table 4 describes the tools and challenges in developing small-molecule therapeutics targeting RNA.

[kntkb]

Analog of Rasdiplam, SMN-C5, stabilize adenosine bulge at the exon 7–intron junction acting as a molecular glue for the ternary complex formed with U1 snRNP.

https://www.rcsb.org/structure/4PJO https://www.cresset-group.com/about/news/target-rna/

[kntkb]

Lack of buried surface area to drive selective interactions could be overcome by binding to multiple structures by simultaneously binding to the same target with a single molecule.

[kntkb]

Chem-CLIP

A tool that can be used to define cellular on- and off-targets and evaluate the selectivity on the transcriptome and the proteome; correlate Chem-CLIP with -omics studies to define optimization plan.

reference Mechanistic studies of a small-molecule modulator of SMN2 splicing