α,α,-Dimethyl-4-[2-methyl-8-[2-(3-pyridinyl)ethynyl]-1H-imidazo[4,5-c]quinolin-1-yl]-benzeneacetonitrile

Uses

NVP-BAG956 acts as a rapamycin inhibitor used in the treatment of various melanomas through cell-induced apoptosis. Also used in antileukemic therapies as a dual PI3K/PDK-1 inhibitor.

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).

IC 50

PI3Kδ: 35 nM (IC₅₀); PI3Kα: 56 nM (IC₅₀); PI3Kγ: 117 nM (IC₅₀); PI3Kβ: 446 nM (IC₅₀); PDK1: 240 nM (IC₅₀); VEGFR1: 2.56 μM (IC₅₀)

storage

Store at -20°C