Targeting Xist with compounds that disrupt RNA structure and X inactivation.

ABSTRACT: Although more than 98% of the human genome is non-coding¹, nearly all of the drugs on the market target one of about 700 disease-related proteins. The historical reluctance to invest in non-coding RNA stems partly from requirements for drug targets to adopt a single stable conformation². Most RNAs can adopt several conformations of similar stabilities. RNA structures also remain challenging to determine³. Nonetheless, an increasing number of diseases are now being attributed to non-coding RNA⁴ and the ability to target them would vastly expand the chemical space for drug development. Here we devise a screening strategy and identify small molecules that bind the non-coding RNA prototype Xist⁵. The X1 compound has drug-like properties an

SUBMITTER: Aguilar R 

PROVIDER: S-EPMC11549687 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature