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Review
. 2025 Sep;182(18):4201-4220.
doi: 10.1111/bph.16027. Epub 2023 Feb 9.

Targeting RNA with small molecules-A safety perspective

Helen L Lightfoot  1 , Graham F Smith  2
Affiliations
Review

Targeting RNA with small molecules-A safety perspective

Helen L Lightfoot et al. Br J Pharmacol. 2025 Sep.

Abstract

RNA is a major player in cellular function, and consequently can drive a number of disease pathologies. Over the past several years, small molecule-RNA targeting (smRNA targeting) has developed into a promising drug discovery approach. Numerous techniques, tools, and assays have been developed to support this field, and significant investments have been made by pharmaceutical and biotechnology companies. To date, the focus has been on identifying disease validated primary targets for smRNA drug development, yet RNA as a secondary (off) target for all small molecule drug programs largely has been unexplored. In this perspective, we discuss structure, target, and mechanism-driven safety aspects of smRNAs and highlight how these parameters can be evaluated in drug discovery programs to produce potentially safer drugs.

Keywords: ribonucleic acid; secondary structure; small molecules.

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References

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