In this work, we performed screening assays and found that AT7519 is a potential drug exerting antitumor activity in GBM through multiple pathways: 1) AT7519 directly targeted on CDKs to arrest the cell cycle at the G1 and G2 phases and inhibit GBM cell proliferation; 2) AT7519 induced GBM cell apoptosis through the intrinsic pathway; 3) AT7519 stimulated pyroptosis by caspase-3-mediated activation of GSDME-N. Here, CASP3 is linked to glioblastoma.