Table 4.

Biological properties of compound 1 and analogues

CompoundAKT inhibition (IC50 μmol/L)
Cytotoxicity (IC50 μmol/L)Log PMetabolic half-life (min)Solubility (μmol/L)Permeability (nm/s)
NIH3T3HT-29Caco2MDCK
1413242.16217.99091
21120141.96228.38334
3>20>20253.29128.69539
4ND>20NI1.2>48012.9238
55>20NI1.513813.1185200
635ND1.9ND<0.1145
  • Abbreviations: NI, not inhibitory for IC50 >100 μmol/L; ND, not determined.

  • NOTE: For each of the analogues, phospho-Ser473 AKT inhibition was measured in either mouse NIH3T3 or human HT-29 colon cancer cells. Cytotoxicity was measured in HT-29 cells. Metabolic stability was measured by incubating with HT-29 cells at the maximum concentration in DMEM at 37°C. The apparent permeability (nm/s) in Caco-2 and MDCK cells was obtained using the QikProp software (Schrodinger Inc.). Values ranged between <25 for poor and >500 for great permeability.