Merck, 5302360001, SKP2 E3 Ligase Inhibitor IV

General description
A cell-permeable dimethylanilinomethylamine compound that inhibits SKP2-dependent cellular p27Kip¹ ubiquitination activity (10 to 30 µM; 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 β-TrCP substrates (c-Jun and β-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 µM), 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 µM drug treatment = 1.38%/66.4% for CD138⁺ vs. 81.3%/94% CD138⁻).
Biochem/physiol Actions
Cell permeable: yes
Primary Target
Skp1/Skp2 interaction
Reversible: yes
Packaging
Packaged under inert gas
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Use only fresh DMSO for reconstitution.
Other Notes
Chen, Q., et al. 2008. Blood111, 4690.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)