Sirt1 Inhibitor VII, Inauhzin - Calbiochem (C15-1305-836)

General description

A cell-permeable phenothiazine derivative that selectively inhibits SirT1 (IC₅₀ ≤2.0 µM), but not SirT2, SirT3, or HCAC8 (IC₅₀ >50 µM), activity and effectively elevates cellular p53 lysine acetylation (Effective conc. 2 µM), thereby protecting p53 lysine residues from MDM2-mediated ubiquitination without directly inhibiting MDM2 function per se or its activity toward deacetylated p53. Shown to inhibit cancer cell growth in a p53-dependent manner (IC₅₀ = 2.0 and 15.7µM, respectively, against HCT116p53^+/+ and HCT116p53^-/- cells) and synergize with Nutlin-3 (Cat. Nos. 444143, 444151, & 444152) in blocking HCT116p53^+/+ proliferation in vitro (by 29%, 76%, and >98, respectively, with 1 µM INZ alone, 4 µM Nutlin-3 alone, or in combination) and inducing HCT116p53^+/+ apoptosis in mice in vivo (3.5% above control TUNEL staining with either drug treatment alone or 25% with combined treatment; 15 mg INZ/kg via daily i.p; 150 mg Nut-3/kg b.i.d. p.o.).

A cell-permeable phenothiazine derivative that selectively inhibits SirT1 (IC₅₀ ≤2.0 µM), but not SirT2, SirT3, or HCAC8 (IC₅₀ >50 µM), activity. Effectively elevates cellular p53 lysine acetylation (Effective conc. 2 µM), thereby protecting p53 lysine residues from MDM2-mediated ubiquitination without inhibiting MDM2 activity toward deacetylated p53. Shown to inhibit cancer cell growth in a p53-dependent manner (IC₅₀ = 2.0 and 15.7µM, respectively, against HCT116p53^+/+ and HCT116p53^-/- cells) and synergize with Nutlin-3 (Cat. Nos. 444143, 444151, & 444152) in blocking HCT116p53^+/+ proliferation in vitro (1 µM INZ & 4 µM Nutlin-3) and inducing HCT116p53^+/+ apoptosis in mice in vivo (15 mg INZ/kg/d i.p; 150 mg Nut-3/kg/12 h p.o.).

Biochem/physiol Actions

Cell permeable: yes

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Other Notes

Zhang, Q., et al. 2012. EMBO Mol. Med.4, 298.
Zhang, Y., et al. 2012. Cancer Biol. Ther.13, 915

Legal Information

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

Molecular Weight: 469.58. Empirical Formula: C₂₅H₁₉N₅OS₂. Quality Level: 100. Assay: ≥. 98% (HPLC). form: powder. potency: 0.7 . μ. M IC₅₀. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, protect from light. color: beige. solubility: DMSO: 100 . mg/mL. shipped in: wet ice. storage temp.: 2-8°C. Storage Class Code: 11 - Combustible Solids. WGK: WGK 3. Flash Point(F): Not applicable. Flash Point(C): Not applicable.