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Inhibitors Library. RNA-Protein Interaction.

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ChemDiv’s RNA-Protein Interaction Inhibitors Library contains 2,111 compounds.

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.

Targeting RBPs with small-molecule inhibitors is still an emerging field in comparison with the targeting of other protein classes, such as G-protein-coupled receptors, ion channels and kinases. In addition to directly modulating the biological activities of the target RBP, small-molecule inhibitors of RBPs can be used to indirectly modulate the interacting RNAs for which small molecules are not available or as an orthogonal approach to target specific protein–RNA interactions for which other modulating ligands are available. Rapid progress occurred in the understanding of the complex regulatory network of protein–RNA interactions and the molecular mechanisms underlying the functions of the different classes of RBPs and in the development of new biochemical and cellular assays for hit validation; consequently, small-molecule modulators of many previously unligandable RBPs have been reported. Small-molecule inhibitors of emerging classes of RBPs, represented by the miRNA-binding protein LIN28, the dsRNA-binding or ssRNA-binding TLRs and the crRNA-binding Cas proteins, have been already identified. [1]

[1] P. Wu, “Inhibition of RNA-binding proteins with small molecules,” Nat. Rev. Chem., vol. 4, no. 9, pp. 441–458, 2020, doi: 10.1038/s41570-020-0201-4.

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