%0 Journal Article
%A Joseph, Benjamin Philipp
%A Weber, Verena
%A Knüpfer, Lisa
%A Giorgetti, Alejandro
%A Alfonso-Prieto, Mercedes
%A Krauß, Sybille
%A Carloni, Paolo
%A Rossetti, Giulia
%T Low Molecular Weight Inhibitors Targeting the RNA-Binding Protein HuR
%J International journal of molecular sciences
%V 24
%N 17
%@ 1422-0067
%C Basel
%I Molecular Diversity Preservation International
%M FZJ-2023-03195
%P 13127 -
%D 2023
%X The 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 37685931
%U <Go to ISI:>//WOS:001061141200001
%R 10.3390/ijms241713127
%U https://juser.fz-juelich.de/record/1010687