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Principles for targeting RNA with drug-like small molecules
- Source :
- Nature Reviews Drug Discovery
- Publication Year :
- 2018
-
Abstract
- RNA molecules are essential for cellular information transfer and gene regulation, and RNAs have been implicated in many human diseases. Messenger and non-coding RNAs contain highly structured elements, and evidence suggests that many of these structures are important for function. Targeting these RNAs with small molecules offers opportunities to therapeutically modulate numerous cellular processes, including those linked to 'undruggable' protein targets. Despite this promise, there is currently only a single class of human-designed small molecules that target RNA used clinically - the linezolid antibiotics. However, a growing number of small-molecule RNA ligands are being identified, leading to burgeoning interest in the field. Here, we discuss principles for discovering small-molecule drugs that target RNA and argue that the overarching challenge is to identify appropriate target structures - namely, in disease-causing RNAs that have high information content and, consequently, appropriate ligand-binding pockets. If focus is placed on such druggable binding sites in RNA, extensive knowledge of the typical physicochemical properties of drug-like small molecules could then enable small-molecule drug discovery for RNA targets to become (only) roughly as difficult as for protein targets.
- Subjects :
- 0301 basic medicine
Drug
media_common.quotation_subject
Druggability
Computational biology
Biology
Ligands
Article
Small Molecule Libraries
03 medical and health sciences
Drug Discovery
Animals
Humans
Binding site
media_common
Regulation of gene expression
Pharmacology
Binding Sites
Drug discovery
RNA
Proteins
General Medicine
Small molecule
Anti-Bacterial Agents
030104 developmental biology
Function (biology)
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Nature Reviews Drug Discovery
- Accession number :
- edsair.doi.dedup.....d8c811dd9a05330938e887116a96ed77