obatoclax mesylate + temozolomide

**obatoclax mesylate + temozolomide** is a combination therapy composed of obatoclax mesylate, a pan-Bcl-2 family inhibitor that targets anti-apoptotic proteins (notably BCL2 and MCL1), and temozolomide, an oral alkylating agent that induces DNA damage and apoptosis in tumor cells. Obatoclax mesylate augments apoptotic cell death by inhibiting multiple Bcl-2 family members, thereby facilitating cell sensitivity to cytotoxic agents. Temozolomide exerts its chemotherapeutic effect primarily via methylation of guanine residues, leading to DNA strand breaks and apoptosis. The combination has been studied in clinical trials for metastatic melanoma and investigated in glioblastoma models. The mechanism of synergy includes enhanced apoptosis and cell cycle arrest, with associated ER-stress pathway modulation (PERK/ATF-4/CHOP axis)[1][2][3][4][5].