Evidence map›Paper›PMID 37685931›Full record

ArticleInternational journal of molecular sciences2023

Low Molecular Weight Inhibitors Targeting the RNA-Binding Protein HuR.

Benjamin Philipp Joseph, Verena Weber, Lisa Knüpfer, Alejandro Giorgetti, Mercedes Alfonso-Prieto, Sybille Krauß, Paolo Carloni, Giulia Rossetti

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Benjamin Philipp JosephInstitute for Neuroscience and Medicine and Institute for Advanced Simulations (INM-9/IAS-5), Computational Biomedicine, Forschungszentrum Jülich, 52425 Jülich, Germany.
Verena WeberInstitute for Neuroscience and Medicine and Institute for Advanced Simulations (INM-9/IAS-5), Computational Biomedicine, Forschungszentrum Jülich, 52425 Jülich, Germany.
Lisa KnüpferInstitute of Biology, University of Siegen, 57076 Siegen, Germany.
Alejandro GiorgettiInstitute for Neuroscience and Medicine and Institute for Advanced Simulations (INM-9/IAS-5), Computational Biomedicine, Forschungszentrum Jülich, 52425 Jülich, Germany.
Mercedes Alfonso-PrietoInstitute for Neuroscience and Medicine and Institute for Advanced Simulations (INM-9/IAS-5), Computational Biomedicine, Forschungszentrum Jülich, 52425 Jülich, Germany.ORCID 0000-0003-4509-4517
Sybille KraußInstitute of Biology, University of Siegen, 57076 Siegen, Germany.
Paolo CarloniInstitute for Neuroscience and Medicine and Institute for Advanced Simulations (INM-9/IAS-5), Computational Biomedicine, Forschungszentrum Jülich, 52425 Jülich, Germany.ORCID 0000-0002-9010-0149
Giulia RossettiInstitute for Neuroscience and Medicine and Institute for Advanced Simulations (INM-9/IAS-5), Computational Biomedicine, Forschungszentrum Jülich, 52425 Jülich, Germany.ORCID 0000-0002-2032-4630

Funding

German Federal Ministry of Education and Research (BMBF) 01DP19004
6 · The paper itself

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.

Indexed as

BenzoatesBiological AssayELAV-Like Protein 1Cell NucleusHumansMolecular WeightRNA-Binding ProteinsBenzoatesELAV-Like Protein 1RNA-Binding Proteinshigh-throughput virtual screeninghuman antigen R (HuR)RNA-binding proteinRNA pulldown assaysmall molecule inhibitors

Identifiers

PMID37685931
PMCPMC10488267

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.