Researchers described new imidazotetrazine derivatives that restore sensitivity in glioblastoma models resistant to temozolomide, the longstanding backbone chemotherapy for GBM. Preclinical data show that the compounds bypass established resistance mechanisms and induce tumor cell death in resistant lines and animal models. The chemistry revives an older scaffold with targeted modifications to counteract resistance biology. Translation will require IND-enabling toxicology and clear differentiation on safety and brain‑penetrant pharmacokinetics before clinical testing, but the work provides a new candidate class to challenge recurrent GBM.