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@ARTICLE{Joseph:1010687,
author = {Joseph, Benjamin Philipp and Weber, Verena and Knüpfer,
Lisa and Giorgetti, Alejandro and Alfonso-Prieto, Mercedes
and Krauß, Sybille and Carloni, Paolo and Rossetti, Giulia},
title = {{L}ow {M}olecular {W}eight {I}nhibitors {T}argeting the
{RNA}-{B}inding {P}rotein {H}u{R}},
journal = {International journal of molecular sciences},
volume = {24},
number = {17},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {FZJ-2023-03195},
pages = {13127 -},
year = {2023},
abstract = {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.},
cin = {IAS-5 / INM-9},
ddc = {540},
cid = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524) / 5252 - Brain Dysfunction and Plasticity
(POF4-525)},
pid = {G:(DE-HGF)POF4-5241 / G:(DE-HGF)POF4-5252},
typ = {PUB:(DE-HGF)16},
pubmed = {37685931},
UT = {WOS:001061141200001},
doi = {10.3390/ijms241713127},
url = {https://juser.fz-juelich.de/record/1010687},
}