Table 2.
IC50 values of indazole series Y4 against wt and as Akt1/2/3
| ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Akt variants IC50 (nM) |
||||||||||||
| Compd | Scheme | R1 | R2 | Akt1-as1 | Akt1-as2 | wtAkt1 | Akt2-as1 | Akt2-as2 | wtAkt2 | Akt3-as1 | Akt3-as2 | wtAkt3 |
| Z(A-443654) | 1 | H– | Me– | ND | ND | 3 | ND | ND | 30 | 30 | ND | 51 |
| Y4a | 2 | Me– | H– | 240 | 100 | >1000 | >1000 | >1000 | >1000 | >1000 | >1000 | >1000 |
| Y4b | 2 | Et– | H– | 860 | 25 | 570 | >1000 | 930 | >1000 | >1000 | 770 | >1000 |
| Y4c | 4 | nPr– | H– | 330 | 6 | >1000 | >1000 | 110 | >1000 | >1000 | 63 | >1000 |
| Y4d | 3 | nBu– | H– | 350 | 4 | >1000 | >1000 | 43 | >1000 | 530 | 33 | >1000 |
| Y4e | 5 | iBu– | H– | >1000 | 6 | >1000 | >1000 | 19 | >1000 | >1000 | 28 | >1000 |
| Y4f | 4 | nPen– | H– | 380 | 26 | >1000 | >1000 | 58 | >1000 | 750 | 34 | >1000 |
| Y4g | 5 | iPen– | H– | 270 | 17 | >1000 | >1000 | 35 | >1000 | 300 | 25 | >1000 |
| Y4h | 5 | PhCH2CH2– | H– | 560 | 34 | >1000 | >1000 | 100 | >1000 | 630 | 50 | >1000 |
| Y4i | 2 | Cl– | H– | 320 | 87 | 720 | >1000 | 700 | >1000 | >1000 | >1000 | >1000 |
| Y4j | 6 | Et– | Me– | 270 | 17 | 740 | >1000 | 200 | >1000 | 900 | 110 | >1000 |
| Y4k (PrlDZ) | 7 | nPr– | Me– | 56 | 2.8 | >1000 | >1000 | 31 | >1000 | 360 | 13 | >10 000 |
| Y4l | 7 | iBu– | Me– | 720 | 6.6 | >1000 | >1000 | 6.7 | >1000 | >1000 | 25 | >10 000 |