Treating glioblastoma with brain-penetrating molecule
Survival rate of glioblastoma is less than 3 years hance there is an urgent need for therapeutic agent to prevent the mortality.
The researchers identified a small compound, gliocidin, that kills glioblastoma cells while sparing non-tumor cells. Gliocidin inhibits inosine monophosphate dehydrogenase 2 (IMPDH2) and reduces intracellular guanine nucleotide levels, causing nucleotide imbalance, replication stress and tumor cell death.
Nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) anabolizes gliocidin into its tumoricidal metabolite, gliocidin–adenine dinucleotide (GAD). The authors show that gliocidin penetrates the blood–brain barrier and extends the survival of mice with orthotopic glioblastoma.
They also demonstrate that DNA alkylating agent temozolomide induces Nmnat1 expression, causing synergistic tumor cell killing.
https://www.nature.com/articles/s41586-024-08224-z
https://sciencemission.com/Gliocidin-is-a-nicotinamide-mimetic-prodrug-that-targets-glioblastoma
