Compound-401

Compound 401 is an inhibitor of DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR; IC50s = 0.28 and 5.3 µM, respectively). It is selective for DNA-PK and mTOR over PI3K, ATM, and ATR (IC50s = >100 µM for all). Compound 401 (10 µM) inhibits phosphorylation of the mTOR targets S6K1 and Akt in Rat-1 fibroblasts and in M059J glioma cells that lack DNA-PK. It inhibits proliferation of mouse embryonic fibroblasts (MEFs) lacking tuberous sclerosis complex 1 (TSC1-/-; IC50 = 2 µM), a complex associated with hamartomas that display hyperactive mTOR signaling, but not TSC1+/+...