Table 1.
Biochemical evaluation of regioisomeric covalent‐allosteric Akt inhibitors with the Akt isoforms.
|
|
|
|
Akt1wt |
Akt2wt |
Akt3wt |
Selectivity α |
|
|---|---|---|---|---|---|---|---|
|
# |
R1 |
R2 |
IC50 [nm] |
IC50 [nm] |
IC50 [nm] |
Akt1/Akt2 |
Akt1/Akt3 |
|
capivasertib |
|
|
1±0.1 |
5±0.4 |
8±1 |
3 |
4 |
|
MK‐2206 |
|
|
10±2 |
157±45 |
951±291 |
10 |
59 |
|
borussertib |
|
‐acryl |
1±0.3 |
56±1 |
618±24 |
56 |
618 |
|
13 a |
|
‐H |
319±166 |
>20 000 |
>20 000 |
– |
– |
|
15 a |
‐acryl |
38±6 |
1569±302 |
>20 000 |
41 |
– |
|
|
14 a |
‐H |
3206±1353 |
11 541±1105 |
>20 000 |
4 |
– |
|
|
16 a |
‐acryl |
39±5 |
13 030±1147 |
>20 000 |
334 |
– |
|
|
13 b |
|
‐H |
5415±1695 |
>20 000 |
>20 000 |
– |
– |
|
15 b |
‐acryl |
490±77 |
>20 000 |
>20 000 |
– |
– |
|
|
14 b |
‐H |
12 834±2469 |
1237±142 |
>20 000 |
0.1 |
– |
|
|
16 b |
‐acryl |
1140±576 |
119±9 |
16 316±4855 |
0.1 |
14 |
|
|
13 c |
|
‐H |
5194±1587 |
>20 000 |
>20 000 |
– |
– |
|
15 c |
‐acryl |
381±116 |
>20 000 |
>20 000 |
– |
– |
|
|
14 c |
‐H |
15 590±3125 |
>20 000 |
17 701±4069 |
– |
1 |
|
|
16 c |
‐acryl |
813±159 |
5033±1061 |
1277±233 |
6 |
2 |
|
