Gliocidin is a nicotinamide-mimetic prodrug that targets glioblastoma.

ABSTRACT: Glioblastoma is incurable and in urgent need of improved therapeutics¹. Here we identify a small compound, gliocidin, that kills glioblastoma cells while sparing non-tumour replicative cells. Gliocidin activity targets a de novo purine synthesis vulnerability in glioblastoma through indirect inhibition of inosine monophosphate dehydrogenase 2 (IMPDH2). IMPDH2 blockade reduces intracellular guanine nucleotide levels, causing nucleotide imbalance, replication stress and tumour cell death². Gliocidin is a prodrug that is anabolized into its tumoricidal metabolite, gliocidin-adenine dinucleotide (GAD), by the enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) of the NAD⁺ salvage pathway. The cryo-electron microscopy structure of GAD together with IMP

SUBMITTER: Chen YJ 

PROVIDER: S-EPMC11665509 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature