RIPGBM is a prodrug form of the pro-apoptotic compound cRIPGBM.1 It is converted to cRIPGBM in GBM-1 glioblastoma multiforme (GBM) cancer stem cells (CSCs) but not primary human lung fibroblasts (HLFs). RIPGBM induces apoptosis in GBM CSCs (EC50 = ≤500 nM) and selectively reduces survival of GBM-1 cells (EC50 = 0.22 μM) over human neural stem cells, primary human astrocytes, and primary HLFs (EC50s = 1.7, 2.9, and 3.5 μM, respectively). It reduces tumor growth in a GBM mouse xenograft model using patient-derived GBM-39 cells engineered to express IR fluorescent protein 720 (IRFP720) when administered at a dose of 50 mg/kg twice per day.
1.Lucki, N.C., Villa, G.R., Vergani, N., et al.A cell type-selective apoptosis-inducing small molecule for the treatment of brain cancerProc. Natl. Acad. Sci. USA116(13)6435-6440(2019)