1Radiology, University of California San Francisco, San Francisco, CA, United States, 2Neurological Surgery, University of California San Francisco, San Francisco, CA, United States
Mutations in IDH1 are predominant in low-grade gliomas, and
inhibitors of the mutant IDH1 enzyme are under investigation as therapeutic
agents. Beyond 2-HG production, the IDH1 mutation also induces a broader
pattern of 1H-MRS-detectable metabolic alterations. In this study,
we investigated whether inhibiting mutant IDH1 using AGI-5198 reverses the
metabolic reprogramming observed in IDH1 mutant glioma cells. Our results
indicate that AGI-5198 treatment, while completely inhibiting 2-HG production,
nevertheless only partially reverses other metabolic alterations and results in
a moderate effect on clonogenicity of IDH1 mutant cells.