TY  - JOUR
AU  - Joseph, Benjamin Philipp
AU  - Weber, Verena
AU  - Knüpfer, Lisa
AU  - Giorgetti, Alejandro
AU  - Alfonso-Prieto, Mercedes
AU  - Krauß, Sybille
AU  - Carloni, Paolo
AU  - Rossetti, Giulia
TI  - Low Molecular Weight Inhibitors Targeting the RNA-Binding Protein HuR
JO  - International journal of molecular sciences
VL  - 24
IS  - 17
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - FZJ-2023-03195
SP  - 13127 -
PY  - 2023
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 37685931
UR  - <Go to ISI:>//WOS:001061141200001
DO  - DOI:10.3390/ijms241713127
UR  - https://juser.fz-juelich.de/record/1010687
ER  -