5.30236

SKP2 E3 Ligase Inhibitor IV

• Synonym(e): SKP2 E3 Ligase Inhibitor IV, CRL1 ^SKP2 Inhibitor IV, p21/Cip1/Waf1 Activator IV, p27/Kip1 Activator IV, S-phase Kinase-associated Protein 2 Inhibitor IV; SCF ^SKP2 Inhibitor IV, (±)-4-((3-(2,2-Dimethyltetrahydro-2H-pyran-4-yl)-4-phenylbutylamino)methyl)-N,N
• Empirische Formel (Hill-System): C₂₆H₃₈N₂O · 2HCl
• CAS-Nummer: 634908-46-6
• Molekulargewicht: 467.51
• UNSPSC-Code: 12352200
• NACRES: NA.77

Eigenschaften

• Assay: ≥95% (HPLC)
• Qualitätsniveau: 100
• Form: solid
• Hersteller/Markenname: Calbiochem^®
• Lagerbedingungen: OK to freeze; protect from light
• Farbe: white
• Löslichkeit: DMSO: 100 mg/mL
• Lagertemp.: 2-8°C

Beschreibung

Allgemeine Beschreibung

A cell-permeable dimethylanilinomethylamine compound that inhibits SKP2-dependent cellular p27^Kip1 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 SCF^SKP2 substrates (p21^Cip1, p27^Kip1, and p57^Kip2) 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^-).

A cell-permeable dimethylanilinomethylamine compound that inhibits SKP2-dependent p27^Kip1 ubiquitination (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 SCF^SKP2 substrates in multiple myeloma RPMI 8226 cells without affecting cellular levels of Fbw7 or β-TrCP substrate (c-Jun and β-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 µM drug treatment = 1.38%/66.4% for CD138⁺ vs. 81.3%/94% CD138^-).

Biochem./physiol. Wirkung

Cell permeable: yes

Primary Target
Skp1/Skp2 interaction

Reversible: yes

Verpackung

Packaged under inert gas

Warnhinweis

Toxicity: Standard Handling (A)

Rekonstituierung

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.

Sonstige Hinweise

Chen, Q., et al. 2008. Blood111, 4690.

Rechtliche Hinweise

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

Sicherheitshinweise

• Lagerklassenschlüssel: 11 - Combustible Solids
• WGK: WGK 3
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable