Table 3. Inhibition of AKT phosphorylation in cell-based assays.
| Cell line |
IC50(nM)a |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
p-AKTT308 |
p-AKTS473 |
|||||||||||
|
TGX-221 |
BYL-719 |
TGX-221 |
BYL-719 |
|||||||||
| n=1 | n=2 | mean | n=1 | n=2 | mean | n=1 | n=2 | mean | n=1 | n=2 | mean | |
| PC-3 | − | − | − | − | − | − | 15.55 | 37.9 | 26.7 | >10000b | >10000b | >10000b |
| LN-18 | 20.88 | 11.44 | 16.2 | 950.7 | 3792 | 2374.4 | 23.93 | 32.58 | 28.3 | 2165 | 1647 | 1906 |
| NCI-H460 | — | — | — | — | — | — | >30000b | >30000b | >30000b | 100.3 | 118.7 | 109.5 |
—, Not done.
a
Levels of phospho-AKTT308 and S473 were measured in cell lysates treated with a range of concentrations of the indicated compound in 0.1% DMSO (PC-3 & LN-18 cells) or 0.3% DMSO (NCI-H460) normalized to the level of total AKT and expressed as a percentage of DMSO control. IC50 values were generated from independent experiments (n) performed in duplicate by non-linear curve fit using Prism software (GraphPad, SD).
b
Top concentration tested in assay.