Survivin Inhibitor III, LLP-3

Cell permeable: yes

Primary Target
survivin

Reversible: yes

Toxicity: Standard Handling (A)

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.

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

Packaged under inert gas

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

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