Evidence map›Paper›PMID 40185715›Full record

ArticleCell death & disease2025

Generation and validation of a novel multitarget small molecule in glioblastoma.

Aizpea Artetxe-Zurutuza, Nerea Iturrioz-Rodriguez, Joseba Elizazu, Mireia Toledano-Pinedo, Alicia Porro-Pérez, Irati De Goñi, Alejandro Elua-Pinin, Linda Schäker-Hübner, Mikel Azkargorta, Felix Elortza and 7 more

Abstract read
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Pharmaceuticals (Basel, Switzerland) · 2025
    Article
  3. Article
  4. 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

17 authors.

Aizpea Artetxe-ZurutuzaCellular Oncology group, Biogipuzkoa (Biodonostia) Health Research Institute, San Sebastian, Spain.
Nerea Iturrioz-RodriguezCellular Oncology group, Biogipuzkoa (Biodonostia) Health Research Institute, San Sebastian, Spain.ORCID http://orcid.org/0000-0003-3698-9570
Joseba ElizazuCellular Oncology group, Biogipuzkoa (Biodonostia) Health Research Institute, San Sebastian, Spain.ORCID http://orcid.org/0000-0002-6859-0970
Mireia Toledano-PinedoLaboratory of Medicinal Chemistry (Institute of General Organic Chemistry, CSIC), Madrid, Spain.
Alicia Porro-PérezLaboratory of Medicinal Chemistry (Institute of General Organic Chemistry, CSIC), Madrid, Spain.
Irati De GoñiCellular Oncology group, Biogipuzkoa (Biodonostia) Health Research Institute, San Sebastian, Spain.
Alejandro Elua-PininCellular Oncology group, Biogipuzkoa (Biodonostia) Health Research Institute, San Sebastian, Spain.
Linda Schäker-HübnerDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Mikel AzkargortaProteomics Platform, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), CIBERehd, Derio, Spain.
Felix ElortzaProteomics Platform, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), CIBERehd, Derio, Spain.
Isabel IriepaAlcala University, Department of Organic and Inorganic Chemistry, Andrés M. del Río Chemistry Research Institute (IQAR); and DISCOBAC group, Castilla-La Mancha Health Research Institute (IDISCAM), Madrid, Spain.
Francisco Lòpez-MuñozFaculty of Health Sciences-HM Hospitals, Camilo José Cela University; HM Hospitals Health Research Institute; Neuropsychopharmacology Unit, "Hospital 12 de Octubre" Research Institute, Madrid, Spain.
Veronica Moncho-AmorCellular Oncology group, Biogipuzkoa (Biodonostia) Health Research Institute, San Sebastian, Spain.
Finn K HansenDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Nicolás SampronCellular Oncology group, Biogipuzkoa (Biodonostia) Health Research Institute, San Sebastian, Spain.
Jose Luis Marco-ContellesLaboratory of Medicinal Chemistry (Institute of General Organic Chemistry, CSIC), Madrid, Spain.
Ander MatheuCellular Oncology group, Biogipuzkoa (Biodonostia) Health Research Institute, San Sebastian, Spain. ander.matheu@biodonostia.org.

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) GRK2873Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación) PID2019-105813RB-C21Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III) DTS24/00153Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III) PI22/01905
6 · The paper itself

Abstract

The development of multitarget small molecules (MSMs) has emerged as a powerful strategy for the treatment of multifactorial diseases such as cancer. Glioblastoma is the most prevalent and malignant primary brain tumor in adults, which is characterized by poor prognosis and a high heterogeneity. Current standards of treatment present limited effectiveness, as patients develop therapy resistance and recur. In this work, we synthesized and characterized a novel multi-target molecule (named DDI199 or contilistat), which is a polyfunctionalized indole derivative developed by juxtaposing selected pharmacophoric moieties of the parent compounds Contilisant and Vorinostat (SAHA) to act as multifunctional ligands that inhibit histone deacetylases (HDACs), monoamine oxidases (MAOs) and cholinesterases (ChEs), and modulate histamine H3 (H3R) and Sigma 1 Receptor (S1R) receptors. DDI199 exerts high cytotoxic activity in conventional glioblastoma cell lines and patient-derived glioma stem cells in vitro. Importantly, it significantly reduces tumor growth in vivo, both alone and in combination with temozolomide (TMZ). The comparison with SAHA showed higher target specificity and antitumor activity of the new molecule. Transcriptomic and proteomic analyses of patient-derived glioma stem cells revealed a deregulation in cell cycle, DNA remodeling and neurotransmission activity by the treatment with DDI199. In conclusion, our data reveal the efficacy of a novel MSM in glioblastoma pre-clinical setting.

Indexed as

Antineoplastic AgentsBrain NeoplasmsGlioblastomaIndolesAnimalsCell Line, TumorCell ProliferationHistone Deacetylase InhibitorsHumansMiceNeoplastic Stem CellsTemozolomideVorinostatXenograft Model Antitumor AssaysAntineoplastic AgentsHistone Deacetylase InhibitorsIndolesTemozolomideVorinostat

Identifiers

PMID40185715
PMCPMC11971462

What OpenQuestion holds

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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.