<h4>Background</h4>Temozolomide (TMZ) resistance in glioblastoma (GBM) remains a critical barrier to treatment success, driven by O<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT) overexpression, glioma stem cell (GSC) persistence, and redox adaptation.<h4>Methods</h4>We developed cp8, a first-in-class abiraterone-based histone deacetylase (HDAC) inhibitor, to simultaneously target these resistance mechanisms. Here, HDAC9 is linked to glioma.