Evidence map›Paper›PMID 41213941›Full record

ArticleCell death discovery2025

Identification of a novel minor-groove DNA binder that represses mitochondrial gene expression and induces apoptosis in highly aggressive leiomyosarcoma cells.

Eleonora Malavasi, Raffaella Picco, Showmeya Mallavarapu, Martina Minisini, Francesca D'Este, Alessio Bertozzo, Lidia Giuliani, Roberta Astolfi, Monica Chinellato, Giacomo Bettin and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

14 authors.

Eleonora MalavasiDepartment of Medicine, Lab of Epigenomics, Università degli Studi di Udine, Udine, 33100, Italy.ORCID http://orcid.org/0000-0002-6689-230X
Raffaella PiccoDepartment of Medicine, Lab of Epigenomics, Università degli Studi di Udine, Udine, 33100, Italy.
Showmeya MallavarapuDepartment of Medicine, Lab of Epigenomics, Università degli Studi di Udine, Udine, 33100, Italy.ORCID http://orcid.org/0000-0002-3339-3811
Martina MinisiniDepartment of Medicine, Lab of Epigenomics, Università degli Studi di Udine, Udine, 33100, Italy.
Francesca D'EsteDepartment of Medicine, Lab of Epigenomics, Università degli Studi di Udine, Udine, 33100, Italy.ORCID http://orcid.org/0000-0001-7550-6135
Alessio BertozzoDepartment of Medicine, Lab of Epigenomics, Università degli Studi di Udine, Udine, 33100, Italy.
Lidia GiulianiRome Center for Molecular Design, Department of Drug Chemistry and Technology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.
Roberta AstolfiRome Center for Molecular Design, Department of Drug Chemistry and Technology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.
Monica ChinellatoDepartment of Biology, University of Padua, Via U. Bassi 58, 35131, Padova, Italy.
Giacomo BettinDepartment of Medicine, Lab of Epigenomics, Università degli Studi di Udine, Udine, 33100, Italy.
Marco BortoluzziDepartment of Molecular Sciences and Nanosystems, Ca' Foscari University of Venice, Via Torino 155, 30172, Mestre, Italy.
Rino RagnoRome Center for Molecular Design, Department of Drug Chemistry and Technology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.
Alessandro AngeliniDepartment of Molecular Sciences and Nanosystems, Ca' Foscari University of Venice, Via Torino 155, 30172, Mestre, Italy.
Claudio BrancoliniDepartment of Medicine, Lab of Epigenomics, Università degli Studi di Udine, Udine, 33100, Italy. claudio.brancolini@uniud.it.ORCID http://orcid.org/0000-0002-6597-5373

Funding

Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) Fellowship Sandra VanniniAssociazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) IG 2021 - ID. 26200Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research) 20228A7JM
6 · The paper itself

Abstract

Leiomyosarcoma (LMS) is an aggressive tumor for which there are few effective therapeutic options. Through a combination of in silico and in vitro screens, we have identified the compound NSC-260594/XMH95 as a promising molecule that selectively induces apoptosis in aggressive LMS cells by upregulating the BH3-only genes PMAP1/NOXA, BIK, HRK and BBC3/PUMA. Similar to the dye Hoechst 33258, XMH95 appears to bind the minor groove of DNA. Unlike Hoechst 33258, XMH95 converts to a fluorescent form only after DNA binding. Furthermore, unlike Hoechst 33258, XMH95 suppresses mitochondrial gene expression and is a more effective inducer of apoptosis. Apart from suppressing mitochondrial genes, XMH95 has many effects on gene expression that it shares with Hoechst 33258. By inhibiting mitochondrial transcription, we show that XMH95 induces apoptosis by impairing both nuclear and mitochondrial transcription. In summary, XMH95 is a novel DNA binder that triggers apoptosis by upregulating multiple BH3-only genes.

Identifiers

PMID41213941
PMCPMC12603272

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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.