A cell-permeable, dihydropyridinone compound that selectively disrupts survivin-Ran interaction in cell-free binding assays (IC50 <0.3uM) and in U87 glioma cells (by 55% in 24h; 20uM) via direct binding at survivin protein-protein interaction interface, while exhibiting much reduced or little potency against survivin-Smac/DIABLO, survivin-survivin, or XIAP-Smac/DIABLO interaction. LLP-3 treatment abrogates neurosphere formation in GMB cultures (IC50 ≤35uM) by selectively depleting CD133+ GSC population via apoptosis induction. TMZ, in comparison, enriches GMB GSC population by preferentially eradicating non-GSC population. LLP-3 is also efficacious in treating human GMB xenograft in mice in vivo (25mg/kg/day via i.p.).
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