Journal
NATURE REVIEWS CHEMISTRY
Volume 4, Issue 9, Pages 441-458Publisher
NATURE RESEARCH
DOI: 10.1038/s41570-020-0201-4
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Funding
- AstraZeneca
- Merck KGaA
- Pfizer Inc.
- Max Planck Society
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Protein-RNA interactions have crucial roles in various cellular activities, which, when dysregulated, can lead to a range of human diseases. The identification of small molecules that target the interaction between RNA-binding proteins (RBPs) and RNA is progressing rapidly and represents a novel strategy for the discovery of chemical probes that facilitate understanding of the cellular functions of RBPs and of therapeutic agents with new mechanisms of action. In this Review, I present a current overview of targeting emerging RBPs using small-molecule inhibitors and recent progress in this burgeoning field. Small-molecule inhibitors that were reported for three representative emerging classes of RBPs, the microRNA-binding protein LIN28, the single-stranded or double-stranded RNA-binding Toll-like receptors and the CRISPR-associated (Cas) proteins, are highlighted from a medicinal-chemistry and chemical-biology perspective. However, although this field is burgeoning, challenges remain in the discovery and characterization of small-molecule inhibitors of RBPs.
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