Abstract
RNA modulation holds potential to ‘drug the undruggable’ targets. RNA-RBP complexes have potential to be druggable targets where small molecules acting as ‘molecular glue’ influence splice modulation of mRNA transcripts. The pockets exist in a moment in time when the RBP and a specific sequence of mRNA comes in proximity for the molecular glue to take action. This scenario is attractive among various approaches because （1）the RBP provides a stable element for the small molecule to interact with, （2）the specific mRNA sequence provides specificity to the molecular glue interaction, and （3）splicing scenarios such as poison exon insertion, or exon skipping may enable potent pharmacological impact via knock down or restoration of function. Rgenta therapeutics leveraged proprietary bioinformatics and a robust suite of RNA-RBP specific med chem techniques to achieve consistent hits on classical undruggable targets, and a methodical approach to optimization.
