Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Characterization and validation of a novel multitarget small-molecule in glioblastoma

ABSTRACT: Characterization and validation of a novel multitarget small-molecule in glioblastoma

PROVIDER: PRJNA1189137 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR31437361_1.fastq.gz	Fastqsanger.gz
	SRR31437361_2.fastq.gz	Fastqsanger.gz
	SRR31437362_1.fastq.gz	Fastqsanger.gz
	SRR31437362_2.fastq.gz	Fastqsanger.gz
	SRR31437363_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 16

Similar Datasets

Characterization and validation of a novel multitarget small-molecule in glioblastoma

Project 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.

2025-04-09 | GSE282561 | GEO

Characterization and validation of a novel multitarget small-molecule in glioblastoma

2025-05-07 | PXD058898 | Pride

Characterization of a new small-molecule inhibitor of HDAC6 in glioblastoma

Project description:Characterization of a new small-molecule inhibitor of HDAC6 in glioblastoma

| PRJNA601982 | ENA

Characterization of a new small-molecule inhibitor of HDAC6 in glioblastoma

Project description:Histone deacetylase 6 (HDAC6) is an epigenetic modifier that is an attractive pharmacological target in cancer. In this work, we show that HDAC6 is elevated in glioblastoma, the most malignant and common brain tumor in adults, and in glioma stem cells. Moreover, we identified a new small-molecule inhibitor of HDAC6, called JOC1, which presents strong sensitivity for HDAC6 inhibition and exerts high cytotoxic activity, alone or in combination with temozolomide. Moreover, it is able to significantly reduce tumor growth in vivo. Transcriptomic analysis of patient derived glioma stem cells revealed an increase in cell differentiation and cell death as well as decrease in cell cycle activity and cell division as relevant cellular pathways whose activities are significantly altered by the treatment with JOC1. In conclusion, our data reveal the efficacy of a novel HDAC6 inhibitor in glioblastoma pre-clinical setting

2020-01-18 | GSE143887 | GEO

Streamlined DNA-encoded small molecule library screening and validation for the discovery of novel chemotypes targeting BET proteins (RNA-seq)

Project description:Targeting aberrant epigenetic programs that drive tumorigenesis is a promising approach to cancer therapy. DNA-encoded small-molecule library (DEL) screening is a core platform technology increasingly used to identify drugs that bind to protein targets. Here, we use DEL screening against bromodomain and extra-terminal motif (BET) proteins to identify inhibitors with new chemotypes, and successfully identified BBC1115 as a selective BET inhibitor. While BBC1115 does not structurally resemble OTX-015, a clinically active pan-BET inhibitor, our intensive computational modeling and biological characterization revealed that BBC1115 binds to BET protein BRD4 and suppresses aberrant cell fate programs. Phenotypically, BBC1115-mediated BET inhibition impaired proliferation in acute myeloid leukemia, pancreatic, and colorectal cancer cells in vitro. Moreover, intravenous administration of BBC1115 inhibited subcutaneous pancreatic and colorectal cancer xenograft growth with minimal toxicity and favorable pharmacokinetic properties in vivo. Since epigenetic regulations are ubiquitously employed across normal and malignant cells, it will be critical to evaluate whether BBC1115 interferes with normal cellular functions. Nonetheless, our study implicates that integrating DEL-based small-molecule compound screening and multi-step biological validation represents a reliable strategy to discover new chemotypes with selectivity, efficacy, and safety profiles for targeting proteins involved in epigenetic regulation in human malignancies.

2023-02-16 | GSE225342 | GEO

Streamlined DNA-encoded small molecule library screening and validation for the discovery of novel chemotypes targeting BET proteins (ChIP-seq)

2023-02-16 | GSE225339 | GEO

The FFPE samples of the primary vs. recurrent glioblastoma validation cohort

Project description:The FFPE samples of the primary vs. recurrent glioblastoma validation cohort

2022-08-08 | PXD035867 |

Epigenetic characterization of glioblastoma stem cells

Project description:Epigenetic characterization of glioblastoma stem cells

| PRJNA430732 | ENA

Identification and Validation of Small Molecule Inhibitors Targeting FGFR through Molecular Docking-Based Screening

Project description:Identification and Validation of Small Molecule Inhibitors Targeting FGFR through Molecular Docking-Based Screening

| PRJNA1113567 | ENA