Small Molecule Cocktail DLC79 Suppresses Gliomagenesis by Activating Ascl1 and Remodeling Transcriptome.

ABSTRACT: Glioblastoma (GBM) remains incurable due to its invasive growth and therapeutic resistance. While the neurogenic transcription factor-mediated reprogramming of glioma cells has been reported, pharmacological reprogramming offers a promising alternative due to its potential advantages for clinical translation. Using phenotype-driven screening, we identified a multi-target small-molecule cocktail DLC79 (DAPT, LDN193189, CHIR99021, I-BET762, and Isx9) that effectively reprograms human glioma cells into neuron-like cells by activating endogenous ASCL1 (174.4-fold) and remodeling the transcriptional landscape. This conversion led to the strong upregulation of neuronal markers (e.g., MAP2 and GAD67) and suppression of glial identity. Functionally, DLC79 treatment inhibited g

SUBMITTER: Mao C 

PROVIDER: S-EPMC12839642 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature