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 <i>ASCL1</i> (174.4-fold) and remodeling the transcriptional landscape. This evidence concerns the gene ASCL1 and glioma.