MDM2 Inhibitor VII, MEL23 - Calbiochem (C15-1303-102)

General description

A cell-permeable tetrahydro-β-carbolinylbarbiturate compound that selectively inhibits the E3 ligase activity of Mdm2-MdmX hetero-complex over that of Mdm2-Mdm2 homo-complex (70.6% vs. 17.6% inhibition, respectively, at 100 µM), without affecting Mdm2-MdmX complex formation or the activity of two other UbcH5C-utilizing ligase complexes Roc1-Cul1 and BRCA1-BARD1. Effectively inhibits ubiquitination and proteasomal degradation of cellular Mdm2 and p53 (effective conc. = 14 µM in U2OS, RKO, and HCT116 cultures) and induce RKO and MEF cell death in a p53- and Mdm2-dependent manner. Unlike Nutlin-3 (Cat. Nos. 444143 & 444151), MEL23 does not interfere with Mdm2-p53 interaction.

A cell-permeable tetrahydro-β-carbolinylbarbiturate compound that selectively inhibits the E3 ligase activity of Mdm2-MdmX hetero-complex over that of Mdm2-Mdm2 homo-complex (70.6% vs. 17.6% inhibition, respectively, with 100 µM inhibitor), without affecting Mdm2-MdmX complex formation or the activity of Roc1-Cul1 and BRCA1-BARD1, two other ligase complexes that also utilize UbcH5C as the Ub-conjugating enzyme. Effectively inhibits Mdm2-MdmX E3 ligase activity-dependent ubiquitination and proteasomal degradation of cellular Mdm2 and p53 (effective conc. = 14 µM in U2OS, RKO, and HCT116 cultures) and prevents DNA damage-induced MdmX degradation in MCF7 cells upon 50 µM etoposide treatment. Shown to induce RKO and MEF cell death in a p53- and Mdm2-dependent manner. Unlike Nutlin-3 (Cat. Nos. 444143 & 444151), MEL23 does not act by interfering Mdm2-p53 interaction.

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Other Notes

Herman, A.G., et al. 2011. Cancer Discovery1, 312.

Legal Information

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

Molecular Weight: 354.40. Empirical Formula: C₁₉H₂₂N₄O₃. Quality Level: 100. Assay: ≥. 95% (HPLC). form: solid. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, protect from light. color: yellow. solubility: DMSO: 2.5 . mg/mL, clear, pale yellow. shipped in: ambient. storage temp.: 2-8°C. SMILES string: OC1: C(C(N(CCCC)C(N1): O): O)C(NCC2)C3: C2C4: C(N3)C: CC: C4. Storage Class Code: 11 - Combustible Solids. WGK: WGK 1. Flash Point(F): Not applicable. Flash Point(C): Not applicable.