QX302

QX302 is a novel small molecule imidazotetrazine derivative developed to address temozolomide (TMZ) resistance in glioblastoma (GBM). As a DNA alkylating agent, it demonstrates high blood-brain barrier (BBB) permeability and exhibits superior potency compared to TMZ in inhibiting the viability of various cancer cell lines, including U251, U87, and T98G glioma cells. QX302 exerts its therapeutic effects by inducing DNA damage, which subsequently triggers cell cycle arrest, apoptosis, and ferroptosis. Proteomic analysis suggests that the drug impacts critical biological pathways such as nucleotide binding, chromatin organization, and DNA repair. Furthermore, QX302 has shown potential in combination therapy by sensitizing cancer cells to PARP inhibitors like olaparib through the modulation of the base excision repair (BER) signaling pathway.