Survivin Inhibitor III, LLP-3

A cell-permeable, bioavailable dihydropyridinone compound that selectively disrupts survivin-Ran interaction (IC₅₀<0.3 µM) in cell-free binding assays and in cells (by 55% in U87 glioma cells after 24 h 20 µM treatment) 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. Survivin and Ran expressions are reported to be upregulated in GSCs (glioma stem cells; CD133-/Nestin-/Sox2-/MELK-positive and TuJ1-negative) when compared to non-GSC (TuJ1-positive) population in patients-derived GMB (Glioblastoma multiforme) cultures and LLP-3 treatment abrogates neurosphere formation in GMB cultures (IC₅₀ ≤35 µM) by selectively depleting CD133+ GSC population (89% drop of CD133+ population vs. 33% drop in CD133- population in GBM528 cultures after 7 d 25 µM treatment) via apoptosis induction. TMZ treatment, in comparison, results in GMB GSC population enrichment by preferentially eradicating non-GSC population. LLP-3 is also efficacious in treating human GMB xenograft in mice in vivo (median survival days = 35 vs. 15.5 with or without treatment; 25 mg/kg/day via i.p.; 5 d/wk for 2 wks starting d10 post GMB xenograft). TMZ (Cat. No. 500609), in comparison, enriches GMB GSC population by preferentially eradicating non-GSC population.

A cell-permeable, dihydropyridinone compound that selectively disrupts survivin-Ran interaction in cell-free binding assays (IC₅₀<0.3 M) and in U87 glioma cells (by 55% in 24 h; 20 M) 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 ≤35 M) by selectively depleting CD133+ GSC population via apoptosis induction. TMZ (Cat. No. 500609), 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 (25 mg/kg/day via i.p.).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Cell permeable: yes

Primary Target
survivin

Reversible: yes

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C. Stock solutions are stable for up to 6 months at -20°C.

Guvenc, H., et al. 2013. Clin. Cancer Res.19, 1.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)