DNA-PK Inhibitor III

A cell-permeable aryl-morpholino compound that acts as a potent, selective, reversible, and ATP-competitive inhibitor of DNA-PK (IC₅₀ = 120 nM) and PI 3-Kinase catalytic subunit p110β (IC₅₀ = 135 nM). It inhibits DNA-PK-mediated cellular DNA DSB (double strand break) repair (EC₅₀ = 68 µM) and enhances DSB-induced antitumor activity both in vitro and in vivo, while exhibiting no cytotoxic effects (up to 50 µM) in the absence of DSBs. It inhibits PI 3-K p110α, p110γ, and p110δ only at much higher concentrations (IC₅₀ = 1.4, 0.88, and 1.0 µM, respectively) and exhibits no effect against a panel of several other kinases, including, Cdk2, Src, PKA, PKC, Chk1, CK1, ATM, and FKBP12, even at concentrations as high as 100 µM.

A cell-permeable, potent, selective, reversible, and ATP-competitive inhibitor of DNA-PK (IC₅₀ = 0.12 µM) and the PI-3 kinase catalytic subunit p110β (IC₅₀ = 0.135 µM). It inhibits DNA-PK-mediated cellular DNA DSB (double strand break) repair (EC₅₀ = 68 µM) and enhances DSB-induced anti-tumor activity both in vitro and in vivo. Exhibits no cytotoxic effects (up to 50 µM) in the absence of DSBs. It inhibits PI3K p110α, p110γ, and p110δ only at much higher concentrations (IC₅₀ = 1.4 µM, 880 nM, and 1 µM, respectively) and does not inhibit a panel of several other kinases, including, Cdk2, Src, PKA, PKC, Chk1, CK1, ATM, and FKBP12, even at concentrations as high as 100 µM.

Cell permeable: yes

Product competes with ATP.

Reversible: yes

Target IC₅₀: 120 nM against DNA-PK

Packaged under inert gas

Toxicity: Carcinogenic / Teratogenic (D)

Kashishian, A., et al. 2004. Mol. Cancer Ther.2, 1257.
Willmore, E., et al. 2004. Blood,103, 4659.

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