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001010687 1001_ $$0P:(DE-Juel1)179040$$aJoseph, Benjamin Philipp$$b0$$ufzj
001010687 245__ $$aLow Molecular Weight Inhibitors Targeting the RNA-Binding Protein HuR
001010687 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2023
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001010687 520__ $$aThe RNA-binding protein human antigen R (HuR) regulates stability, translation, and nucleus-to-cytoplasm shuttling of its target mRNAs. This protein has been progressively recognized as a relevant therapeutic target for several pathologies, like cancer, neurodegeneration, as well as inflammation. Inhibitors of mRNA binding to HuR might thus be beneficial against a variety of diseases. Here, we present the rational identification of structurally novel HuR inhibitors. In particular, by combining chemoinformatic approaches, high-throughput virtual screening, and RNA–protein pulldown assays, we demonstrate that the 4-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl)benzoate ligand exhibits a dose-dependent HuR inhibition effect in binding experiments. Importantly, the chemical scaffold is new with respect to the currently known HuR inhibitors, opening up a new avenue for the design of pharmaceutical agents targeting this important protein.
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001010687 7001_ $$0P:(DE-Juel1)190221$$aWeber, Verena$$b1$$ufzj
001010687 7001_ $$0P:(DE-HGF)0$$aKnüpfer, Lisa$$b2
001010687 7001_ $$0P:(DE-Juel1)165199$$aGiorgetti, Alejandro$$b3$$ufzj
001010687 7001_ $$0P:(DE-Juel1)169976$$aAlfonso-Prieto, Mercedes$$b4
001010687 7001_ $$0P:(DE-HGF)0$$aKrauß, Sybille$$b5$$eCorresponding author
001010687 7001_ $$0P:(DE-Juel1)145614$$aCarloni, Paolo$$b6$$eCorresponding author
001010687 7001_ $$0P:(DE-Juel1)145921$$aRossetti, Giulia$$b7
001010687 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms241713127$$gVol. 24, no. 17, p. 13127 -$$n17$$p13127 -$$tInternational journal of molecular sciences$$v24$$x1422-0067$$y2023
001010687 8564_ $$uhttps://juser.fz-juelich.de/record/1010687/files/ijms-24-13127-v3.pdf$$yOpenAccess
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