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Beschreibung

A cell-permeable dimethylanilinomethylamine compound that inhibits SKP2-dependent cellular p27Kip1 ubiquitination activity (10 to 30 microM, 16 h, in MM1.S myeloma and HeLa cultures) by preventing the incorporation of SKP2 into the Skp1-cullin1-F-box/SCF complex. Selectively induces the accumulation of known SCFSKP2 substrates (p21Cip1, p27Kip1, and p57Kip2) in multiple myeloma RPMI 8226 cells, without inducing HSP-27 phosphorylation or affecting cellular levels of Fbw7 and &beta,-TrCP substrates (c-Jun and &beta,-catenin, respectively) seen with proteasome inhibition by Bortezomib (Cat. No. 504314) treatment. Shown to exhibit antiproliferation activity against 13 myeloma lines (GI50 in 3 d from 4.2 to 13.2 microM), including melphalan-, doxorubicin- and steroid-resistant clones, via autophage-initiated cell death induction in a caspase-3-independent manner, and exhibit cancer-selective cytotoxicity against primary CD138+ malignant cells vs. CD138- nonneoplastic blood cells from MM patient blood (viability in 24 h with/without 5 microM drug treatment = 1.38%/66.4% for CD138+ vs. 81.3%/94% CD138-)., A cell-permeable dimethylanilinomethylamine compound that inhibits SKP2-dependent p27Kip1 ubiquitination (10 to 30 microM, 16 h, in MM1.S myeloma and HeLa cultures) by preventing the incorporation of SKP2 into the Skp1-cullin1-F-box/SCF complex. Selectively induces the accumulation SCFSKP2 substrates in multiple myeloma RPMI 8226 cells without affecting cellular levels of Fbw7 or &beta,-TrCP substrate (c-Jun and &beta,-catenin, respectively) seen with proteasome inhibition by Bortezomib (Cat. No. 504314) treatment. Shown to exhibit cancer-selective cytotoxicity against primary CD138+ malignant cells over CD138- nonneoplastic blood cells from MM patient blood (viability in 24 h with/without 5 microM drug treatment = 1.38%/66.4% for CD138+ vs. 81.3%/94% CD138-).