Evidence map›Paper›PMID 40399488›Full record

ArticleScientific reports2025

Identification of non-charged 7.44 analogs interacting with the NHR2 domain of RUNX1-ETO with improved antiproliferative effect in RUNX-ETO positive cells.

Mohanraj Gopalswamy, David Bickel, Niklas Dienstbier, Jia-Wey Tu, Melina Vogt, Stephan Schott-Verdugo, Sanil Bhatia, Manuel Etzkorn, Holger Gohlke

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Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Mohanraj GopalswamyInstitute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
David BickelInstitute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.ORCID http://orcid.org/0000-0003-0332-8338
Niklas DienstbierDepartment of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.ORCID http://orcid.org/0009-0000-0871-9165
Jia-Wey TuDepartment of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Melina VogtDepartment of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Stephan Schott-VerdugoInstitute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.ORCID http://orcid.org/0000-0003-0735-1404
Sanil BhatiaDepartment of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.ORCID http://orcid.org/0000-0001-6494-7744
Manuel EtzkornInstitute for Physical Biology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.ORCID http://orcid.org/0000-0002-9796-3246
Holger GohlkeInstitute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. gohlke@uni-duesseldorf.de.ORCID http://orcid.org/0000-0001-8613-1447

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The RUNX1/ETO fusion protein is a chimeric transcription factor in acute myeloid leukemia (AML) created by chromosomal translocation t(8;21)(q22;q22). t(8;21) abnormality is associated with 12% of de novo AML cases and up to 40% in the AML subtype M2. Previously, we identified the small-molecule inhibitor 7.44, which interferes with NHR2 domain tetramerization of RUNX1/ETO, restores gene expression down-regulated by RUNX1/ETO, inhibits proliferation, and reduces RUNX1/ETO-related tumor growth in a mouse model. However, despite favorable properties, 7.44 is negatively charged at physiological pH and was predicted to have low to medium membrane permeability. Here, we identified M23, M27, and M10 as non-charged analogs of 7.44 using ligand-based virtual screening, in vivo hit identification, biophysical and in vivo hit validation, and integrative modeling and ADMET predictions. All three compounds interact with the NHR2 domain, have K

Indexed as

Antineoplastic AgentsCore Binding Factor Alpha 2 SubunitLeukemia, Myeloid, AcuteOncogene Proteins, FusionRUNX1 Translocation Partner 1 ProteinAnimalsCell Line, TumorCell ProliferationHumansMiceProtein DomainsAML1-ETO fusion protein, humanAntineoplastic AgentsCore Binding Factor Alpha 2 SubunitOncogene Proteins, FusionRUNX1 protein, humanRUNX1T1 protein, humanRUNX1 Translocation Partner 1 ProteinAcute myeloid leukemiaBiophysical experimentCellular assayLigand-based virtual screeningProtein-protein interaction inhibitorT(8;21)

Identifiers

PMID40399488
PMCPMC12095692

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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.