Abstract #2641

Inhibiting 2-hydroxyglutarate production reverses some, but not all, of the MRS-detectable metabolic markers of mutant IDH1 in glioma

Pavithra Viswanath¹, Russell Pieper², and Sabrina M Ronen¹

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.

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