Table 2.

M3814 potency and selectivity.

AssayIC50 (nmol/L)
DNA-PK, IC50 [10 μmol/L ATP]0.6
DNA-PK, IC50 [1,000 μmol/L ATP]20
Protein kinases panel profiling276/284 not inhibited ≥50% at 1 μmol/L
PIKK family members
 ATM10,000
 ATR2,800
 hPI3Kalpha330
 hPI3Kbeta250
 hPI3Kgamma>1,000
 hPI3Kdelta95
 mTOR>10,000
HU-induced pS345-CHK1>25,000
Bleomycin-induced pT68-CHK2>5,000
Constitutive pS473-AKT in PC33,800
  • Abbreviations: ATM, ataxia-telangiectasia mutated; ATP, adenosine triphosphate; ATR, ATM and rad3-related; CHK, checkpoint kinase; DNA-PK, DNA-dependent protein kinase; HU, hydroxyurea; IC50, half maximal inhibitory concentration; mTOR, mammalian target of rapamycin; PI3K, phosphoinosiditde 3-kinase; PIKK, phosphatidylinositol 3-kinase-related kinase.