biostudies-literatureSoltyka-Krajewska MNational Science Centre in Poland2240https://www.ebi.ac.uk/biostudies/studies/S-EPMC11504489biostudies-literatureUnknown12(10)<h4>Background</h4>One defining feature of various aggressive cancers, including glioblastoma multiforme (GBM), is glycolysis upregulation, making its inhibition a promising therapeutic approach. One promising compound is 2-deoxy-d-glucose (2-DG), a d-glucose analog with high clinical potential due to its ability to inhibit glycolysis. Upon uptake, 2-DG is phosphorylated by hexokinase to 2-DG-6-phosphate, which inhibits hexokinase and downstream glycolytic enzymes. Unfortunately, therapeutic use of 2-DG is limited by poor pharmacokinetics, suppressing its efficacy.<h4>Methods</h4>To address these issues, we synthesized novel halogenated 2-DG analogs (2-FG, 2,2-diFG, 2-CG, and 2-BG) and evaluated their glycolytic inhibition in GBM cells. Our in vitro and computational studies suggest that tBiomedicinesPotent Biological Activity of Fluorinated Derivatives of 2-Deoxy-d-Glucose in a Glioblastoma Model.PMC11504489UMO-2017/25/B/NZ3/00251Pajak-Tarnacka BZiemniak MJaskiewicz ASoltyka-Krajewska MZielinski RKozminski WSkora SWozniak KZawadzka-Kazimierczuk ASiwiak-Niedbalska EPriebe WSkrzypczyk PFokt IfalsePotent Biological Activity of Fluorinated Derivatives of 2-Deoxy-d-Glucose in a Glioblastoma Model.<h4>Background</h4>One defining feature of various aggressive cancers, including glioblastoma multiforme (GBM), is glycolysis upregulation, making its inhibition a promising therapeutic approach. One promising compound is 2-deoxy-d-glucose (2-DG), a d-glucose analog with high clinical potential due to its ability to inhibit glycolysis. Upon uptake, 2-DG is phosphorylated by hexokinase to 2-DG-6-phosphate, which inhibits hexokinase and downstream glycolytic enzymes. Unfortunately, therapeutic use of 2-DG is limited by poor pharmacokinetics, suppressing its efficacy.<h4>Methods</h4>To address these issues, we synthesized novel halogenated 2-DG analogs (2-FG, 2,2-diFG, 2-CG, and 2-BG) and evaluated their glycolytic inhibition in GBM cells. Our in vitro and computational studies suggest that t2024-01-01T00:00:00Z2024 Oct2026-07-08T03:19:02.254Z2025-04-04T11:42:54.363ZS-EPMC115044893945755310.3390/biomedicines12102240