Discovery of a new pyrimidine synthesis inhibitor eradicating glioblastoma-initiating cells.

ABSTRACT:

Background

Glioblastoma-initiating cells (GICs) comprise a tumorigenic subpopulation of cells that are resistant to radio- and chemotherapies and are responsible for cancer recurrence. The aim of this study was to identify novel compounds that specifically eradicate GICs using a high throughput drug screening approach.

Methods

We performed a cell proliferation/death-based drug screening using 10 560 independent compounds. We identified dihydroorotate dehydrogenase (DHODH) as a target protein of hit compound 10580 using ligand-fishing and mass spectrometry analysis. The medical efficacy of 10580 was investigated by in vitro cell proliferation/death and differentiation and in vivo tumorigenic assays.

Results

Among the effective compounds, we identified 10580, which indu

SUBMITTER: Echizenya S 

PROVIDER: S-EPMC7442393 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature