INSOLUTION FOXO1 INHIBITOR AS1842856 (C15-1304-378)

General description

A cell-permeable oxodihydroquinoline that preferentially inhibits the transcription activity of Forkhead box O family member Foxo1 over that of the functionally related Foxo3a and Foxo4 (70%, 20%, and 3% inhibition, respectively, in HepG2-based reporter assays; [AS184256] = 100 nM) in a dose-dependent manner (IC₅₀ = 33 nM) via direct binding of the non-Ser256-phosphorylated/active Foxo1, but not the Ser256-phosphorylated/inactive form of Foxo1. Shown to inhibit gluconeogenesis in rat heptoma Fao cultures (IC₅₀ = 37 and 130 nM against PEPCK and G6Pase mRNA level; IC₅₀ = 43 nM against glucose production) in vitro and in murine liver of both normoglycemic ICR mice (60% and 45% inhibition of hepatic G6Pase and PEPCK mRNA level, respectively; three 100 mg/kg p.o. dosages at 0, 12, 24 h) and diabetic db/db mice (86%, 70%, 56%, 48%, 35%, and 31% inhibition of hepatic G6Pase, ABCG8, ABCG5, PEPCK, IL-1β, and apoCIII mRNA level, respectively; three 100 mg/kg p.o. dosages at 0, 12, 24 h) during a 26-hour fasting period in vivo.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
Foxo1

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Physical form

A 50 mM (5 mg/288 µL) sterile-filtered solution of Foxo1 Inhibitor, AS1842856 (Cat. No. 344355) in DMSO.

Reconstitution

Following initial thaw, aliquot and freeze (-20°C). Aliquots are stable for up to 6 months at -20°C.

Other Notes

Nagashima, T., et al. 2010. Mol. Pharmacol.78, 961.

Legal Information

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

Molecular Weight: 347.38. Empirical Formula: C₁₈H₂₂FN₃O₃. Quality Level: 100. Assay: ≥. 98% (HPLC). form: liquid. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, avoid repeated freeze/thaw cycles, desiccated (hygroscopic), protect from light. storage temp.: −. 70°C. Storage Class Code: 10 - Combustible liquids. WGK: WGK 1. Flash Point(F): 188.6 °F - (refers to pure substance). Flash Point(C): 87 °C - (refers to pure substance).