Compound 401

Research use only, not for human use.

A synthetic inhibitor of DNA-PK also inhibits mTOR (IC50=5.3 uM).

A synthetic inhibitor of DNA-PK also inhibits mTOR (IC50=5.3 uM); no inhibition on p110α/p85α PI3K (>100 uM); blocks the phosphorylation of S6 kinase 1 Thr389 and Akt Ser473 in COS7 cells.

Compound 401 is a potent inhibitor of DNA-PK (IC50=0.28 μM). Compound 401 is reported to be a poor inhibitor of PI3K, ATM, and ATR in vitro, but it is active against mTOR. Compound 401 shows activity against mTOR (IC50=5.3 μM) but not p110α/p85α PI3K (IC50>100 μM). Treatment of cells with Compound 401 blocks the phosphorylation of sites modified by mTOR-Raptor and mTOR-Rictor complexes (ribosomal protein S6 kinase 1 Thr389 and Akt Ser473, respectively). By contrast, there is no direct inhibition of Akt Thr308 phosphorylation, which is dependent on PI3K. Similar effects are also observed in cells that lack DNA-PK. Compound 401 inhibits immunoprecipitated epitope-tagged mTOR or endogenous mTOR in Raptor immunoprecipitates. In both cases, inhibition of 67% or 78% is obtained at 5 μM or 10 μM Compound 401, respectively. By contrast, dose response curves show that the p110α/p85α or p110β/p85α PI3K complexes are poorly inhibited by Compound 401 at these concentrations. The proliferation of TSC1-/- fibroblasts is inhibited in the presence of Compound 401, but TSC1+/+ cells are resistant.

——

Compound-401 | Compound401

Cell Cycle/DNA Damage

DNA-PK

DNA-PK

Cancer

——

168425-64-7

281.3092

C16H15N3O2

>98% (HPLC)

DMSO: 6 mg/mL

O=C1C=C(N2CCOCC2)N=C3N1C=CC4=C3C=CC=C4

4H-Pyrimido[2,1-a]isoquinolin-4-one, 2-(4-morpholinyl)-

(-20℃)

With Ice Pack

≥ 2 years