PXD058898

PXD058898 is an original dataset announced via ProteomeXchange.

Title	Characterization and validation of a novel multitarget small-molecule in glioblastoma
Description	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), 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 5-hydroxytryptamine 6 (5-HT6R) 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 and neurotransmission activity by the treatment with DDI199. In conclusion, our data reveal the efficacy of a novel MSM in glioblastoma pre-clinical setting.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_06:01:10.452.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mikel Azkargorta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-16 02:33:06	ID requested
⏵ 1	2025-05-07 06:01:11	announced

10.1038/s41419-025-07569-1;

Artetxe-Zurutuza A, Iturrioz-Rodriguez N, Elizazu J, Toledano-Pinedo M, Porro-P, é, rez A, De Go, ñ, i I, Elua-Pinin A, Sch, ä, ker-H, ü, bner L, Azkargorta M, Elortza F, Iriepa I, L, ò, pez-Mu, ñ, oz F, Moncho-Amor V, Hansen FK, Sampron N, Marco-Contelles JL, Matheu A, Generation and validation of a novel multitarget small molecule in glioblastoma. Cell Death Dis, 16(1):250(2025) [pubmed]

submitter keyword: Glioblastoma, MSM, glioma stem cells, HDAC, apoptosis, cell cycle

Felix Elortza
contact affiliation	Proteomics Platform CIC bioGUNE Bizkaia Tech. Park Build. 800 48160 Derio (Spain)
contact email	felortza@cicbiogune.es
lab head
Mikel Azkargorta
contact affiliation	Proteomics Platform CIC bioGUNE
contact email	mazkargorta@cicbiogune.es
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD058898

PRIDE project URI

• PRIDE
  1. PXD058898
     1. Label: PRIDE project
     2. Name: Characterization and validation of a novel multitarget small-molecule in glioblastoma