Table 3. SAR of Active-Site Inhibitors with the C40-Carbamate Chemical Handle.

| entry | compound no. | PEG repeats | active-site inhibitor | pS6K IC50 (nM) | p4EBP1 IC50 (nM) | pAKT IC50 (nM) | selectivity |
|---|---|---|---|---|---|---|---|
| 1 | 29 | 8 | MLN | 0.61 | 1.7 | 3.6 | 2.1 |
| 2 | 30 | 8 | “rigid MLN” | 0.19 | 0.42 | 4.7 | 11.2 |
| 3 | 31 | 8 | XL388 | 0.23 | 0.70 | 2.9 | 4.1 |