Researchers reported novel imidazotetrazine derivatives that overcome temozolomide resistance in glioblastoma models, presenting a potential route to address a longstanding therapeutic gap in GBM. The preclinical chemistry showed activity against resistant tumor cells and suggests new avenues for temozolomide‑refractory disease. Complementing chemistry advances, mechanistic work linked HDAC1 phase separation/condensation to temozolomide sensitivity, identifying a biomolecular process that may predict or modulate drug response. Together, the discoveries outline both a candidate chemical strategy and a potential biomarker for resistance management.