Fluorinated NR Enhances NAD+ Depletion in Glioblastoma Therapy: Preclinical Findings

Synopsis

Glioblastoma is one of the most aggressive and treatment-resistant brain cancers, partly because its cells rely heavily on NAD+, a molecule vital for energy production and survival. The drug FK866, which blocks NAD+ synthesis, can slow tumor growth but has limited effectiveness on its own. This study introduces a new approach using fluorinated NAD precursors, specifically F-NR (a modified version of nicotinamide riboside), to amplify FK866’s cancer-killing power. F-NR interferes with the tumor’s NAD+ metabolism, lowering NAD+ levels even further and making glioblastoma cells more vulnerable to FK866. The combination triggers a cascade of effects—severe NAD+ depletion, loss of cellular energy (ATP), and widespread cell death. Researchers also found that SARM1, a protein that breaks down NAD+, is activated by one of F-NR’s metabolites, strengthening this effect. Together, these results reveal a promising strategy to disrupt energy metabolism in glioblastoma cells, offering a new potential therapy for this deadly brain cancer.

Journal

Biology