Modulating microRNA Processing: Enoxacin, the Progenitor of a New Class of Drugs.

Journal of Medicinal Chemistry
Tommaso FelicettiGiuseppe Manfroni

Abstract

The RNA interference (RNAi) process encompasses the cellular mechanisms by which short-noncoding RNAs posttranscriptionally modulate gene expression. First discovered in 1998, today RNAi represents the foundation underlying complex biological mechanisms that are dysregulated in many diseases. MicroRNAs are effector molecules of gene silencing in RNAi, and their modulation can lead to a wide response in cells. Enoxacin was reported as the first and unique small-molecule enhancer of microRNA (SMER) maturation. Herein, the biological activity of enoxacin as SMER is discussed to shed light on its innovative mode of action, its potential in treating different diseases, and the feasibility of using enoxacin as a chemical template for inspiring medicinal chemists. We debate its mechanism of action at the molecular level and the possible impact on future ligand and/or structure-guided chemical optimizations, as well as opportunities and drawbacks associated with the development of quinolones such as SMERs.

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Citations

Mar 7, 2021·International Journal of Molecular Sciences·Rebecca RaueBernhard Brüne
Jun 2, 2021·Journal of Medicinal Chemistry·Farzad Zamani, Takayoshi Suzuki
Jun 2, 2021·Future Medicinal Chemistry·Tommaso Felicetti, Giuseppe Manfroni
Jul 3, 2021·Cancers·Christina PfabNahed El-Najjar

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