Evidence map›Paper›PMID 33266352›Full record

ArticleInternational journal of molecular sciences2020

Identification of a Selective RelA Inhibitor Based on DSE-FRET Screening Methods.

Yoshitomo Shiroma, Go Fujita, Takuya Yamamoto, Ryou-U Takahashi, Ashutosh Kumar, Kam Y J Zhang, Akihiro Ito, Hiroyuki Osada, Minoru Yoshida, Hidetoshi Tahara

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 49% of its field
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

5 citing papers in PubMed, 6 citations in OpenAlex.

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  5. Article
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

10 authors at 4 institutions in 1 country.

Yoshitomo ShiromaDepartment of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Go FujitaDepartment of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Takuya YamamotoDepartment of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Ryou-U TakahashiDepartment of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan.ORCID 0000-0002-9192-2929
Ashutosh KumarLaboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.
Kam Y J ZhangLaboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.ORCID 0000-0002-9282-8045
Akihiro ItoLaboratory of Cell Signaling, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan..
Hiroyuki OsadaChemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.ORCID 0000-0002-3606-4925
Minoru YoshidaChemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Hidetoshi TaharaDepartment of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan.ORCID 0000-0003-3054-4175
Hiroshima University · JPRIKEN Center for Biosystems Dynamics Research · JPRIKEN Center for Sustainable Resource Science · JPTokyo University of Pharmacy and Life Sciences · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nuclear factor-κB (NF-κB) is an important transcription factor involved in various biological functions, including tumorigenesis. Hence, NF-κB has attracted attention as a target factor for cancer treatment, leading to the development of several inhibitors. However, existing NF-κB inhibitors do not discriminate between its subunits, namely, RelA, RelB, cRel, p50, and p52. Conventional methods used to evaluate interactions between transcription factors and DNA, such as electrophoretic mobility shift assay and luciferase assays, are unsuitable for high-throughput screening (HTS) and cannot distinguish NF-κB subunits. We developed a HTS method named DNA strand exchange fluorescence resonance energy transfer (DSE-FRET). This assay is suitable for HTS and can discriminate a NF-κB subunit. Using DSE-FRET, we searched for RelA-specific inhibitors and verified RelA inhibition for 32,955 compounds. The compound A55 (2-(3-carbamoyl-6-hydroxy-4-methyl-2-oxopyridin-1(2H)-yl) acetic acid) selectively inhibited RelA-DNA binding. We propose that A55 is a seed compound for RelA-specific inhibition and could be used in clinical applications.

Indexed as

Binding SitesCell Line, TumorDNADrug Evaluation, PreclinicalFluorescence Resonance Energy TransferHigh-Throughput Screening AssaysHumansModels, MolecularMolecular ConformationMolecular Docking SimulationMolecular Dynamics SimulationMolecular StructureProtein BindingStructure-Activity RelationshipTranscription Factor RelADNARELA protein, humanTranscription Factor RelADNA-binding proteindrug discoveryhigh-throughput screeningNF-κB

Identifiers

PMID33266352
PMCPMC7734590
OpenAlexW3109383563

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.