Biological properties of compound 1 and analogues
| Compound | AKT inhibition (IC50 μmol/L) | Cytotoxicity (IC50 μmol/L) | Log P | Metabolic half-life (min) | Solubility (μmol/L) | Permeability (nm/s) | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| NIH3T3 | HT-29 | Caco2 | MDCK | |||||||
| 1 | 4 | 13 | 24 | 2.1 | 62 | 17.9 | 90 | 91 | ||
| 2 | 11 | 20 | 14 | 1.9 | 62 | 28.3 | 83 | 34 | ||
| 3 | >20 | >20 | 25 | 3.2 | 91 | 28.6 | 95 | 39 | ||
| 4 | ND | >20 | NI | 1.2 | >480 | 12.9 | 23 | 8 | ||
| 5 | 5 | >20 | NI | 1.5 | 138 | 13.1 | 185 | 200 | ||
| 6 | 3 | 5 | ND | 1.9 | ND | <0.1 | 14 | 5 | ||
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.