Evidence map›Paper›PMID 40594510›Full record

ArticleScientific reports2025

Molecular docking and biological evaluation of a novel IWS1 inhibitor for the treatment of human retroperitoneal liposarcoma.

Marina Goryunova, Yiran He, Carson Karakis, Elizaveta K Titerina, Ana I Salazar-Puerta, Sayumi Tahara, Nipin Sp, Neil N Thakkar, Orlando Cómbita-Heredia, Kavya Dathathreya and 8 more

Abstract read
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In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

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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

18 authors.

Marina GoryunovaDepartment of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Yiran HeDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.
Carson KarakisDepartment of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Elizaveta K TiterinaDepartment of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Ana I Salazar-PuertaDepartment of Biomedical Engineering, The Ohio State University, Columbus, OH, USA.
Sayumi TaharaDepartment of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Nipin SpDepartment of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Neil N ThakkarDepartment of Biomedical Engineering, The Ohio State University, Columbus, OH, USA.
Orlando Cómbita-HerediaDepartment of Biomedical Engineering, The Ohio State University, Columbus, OH, USA.
Kavya DathathreyaDepartment of Biomedical Engineering, The Ohio State University, Columbus, OH, USA.
Alessandro La FerlitaDepartment of Internal Medicine, Division of Medical Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Yanping XuDivision of Cardiac Surgery, Department of Surgery, The Ohio State University, Columbus, OH, USA.
Zhentao ZhangDivision of Cardiac Surgery, Department of Surgery, The Ohio State University, Columbus, OH, USA.
Raphael PollockDepartment of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Daniel Gallego-PerezDepartment of Biomedical Engineering, The Ohio State University, Columbus, OH, USA.
Hua ZhuDivision of Cardiac Surgery, Department of Surgery, The Ohio State University, Columbus, OH, USA.
Christopher M HadadDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.
Joal D BeaneDepartment of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA. Joal.Beane@osumc.edu.

Funding

American Cancer Society CSDG-24-1259694-01-RMC
6 · The paper itself

Abstract

IWS1 is a key assembly factor of the RNA polymerase II (RNAPII) elongation complex, and its overexpression is associated with worse outcomes in patients with liposarcoma (LPS). This study aimed to identify compounds that can disrupt the IWS1/Spt6 interaction and assess their biological effects in dedifferentiated LPS (DDLPS). Using the AlphaFold-predicted structure of IWS1, we identified a core binding region (AA 545-694) for its interaction with Spt6. Through molecular modeling and virtual screening, Ketotifen and Desloratadine were predicted as candidate inhibitors. Both were predicted to mimic Spt6 phenylalanine (F217) and disrupt the complex, which was confirmed by co-immunoprecipitation. Functional assays showed that treatment with either compound reduced migration, invasion, and spheroid formation in DDLPS cell lines. Additionally, increased nuclear localization of IWS1 was observed. These findings suggest Ketotifen and Desloratadine as promising inhibitors of the IWS1/Spt6 interaction, with potential applications in reducing the invasive properties of human LPS.

Indexed as

Antineoplastic AgentsLiposarcomaMolecular Docking SimulationTranscription FactorsCell Line, TumorCell MovementHumansLoratadineProtein BindingAntineoplastic AgentsLoratadineTranscription Factors

Identifiers

PMID40594510
PMCPMC12216911

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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.