General description

A cell-permeable imidazoquinoline compound that acts as a potent, reversible, and ATP-competitive PI 3-K/PDK1 dual kinase inhibitor (IC₅₀ = 56, 446, 35, 117, and 245 nM against p110α, p110β, p110δ, p110γ, and PDK1, respectively), displaying much reduced potency against VEGFR1 (IC₅₀ = 2.56 µM) and little or no activity toward a panel of 15 other kinases (IC₅₀ >10 µM). Shown to effectively inhibit the constitutive phosphorylation of PKB (T308 & S473; IC₅₀ ≤45 nM) as well as PKB downstream effectors GSK3β (S9), FKHRL1 (T32), and p70^S6K (T389) in human glioma U87MG and adeonocarcinoma PC3M cultures with PTEN deletion in vitro and retard PC3M-derived tumor growth in mice (by 50%; 75 mg/kg; twice per day p.o.) in vivo. Also reported to exhibit antiproliferative activities against BCRF-ABL- and mutant FLT3-expressing cells either alone or in combination with other PI3K/AKT, mTOR, and tyrosine kinase inhibitors, LY294002 (Cat. Nos. 440202 & 440204), Rapamycin (Cat. No. 553210), and PKC412 (Cat. No. 539648).

Legal Information

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

Other Notes

Marone, R., et al. 2009. Mol. Cancer Res.7, 601.Weisberg, E., et al. 2008. Blood111, 3723.Stauffer, F., et al. 2008. Bioorg. Med. Chem. Lett.18, 1027.

Packaging

5 mg in Glass bottle

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)