Table 2.
The degradation rate (DR) and cellular inhibition (IC50) of designed PROTACs varying the linkers.
 | ||||||
|---|---|---|---|---|---|---|
| Compd. | Linker | DR against Ba/F3T315I (%) |
Cellular inhibition IC50 (nmol/L) |
|||
| 100 nmol/L | 300 nmol/L | K562 | Ba/F3 Bcr-AblWT | Ba/F3 Bcr-AblT315I | ||
| 7g | A, n = 1 | −11.43 | 28.39 | 3.5 ± 0.5 | 20.7 ± 2.4 | 67.5 ± 3.2 |
| 7h | A, n = 3 | 16.86 | 78.34 | 13.7 ± 9.3 | 10.6 ± 2.6 | 83.4 ± 31.6 |
| 7i | A, n = 4 | −22.44 | −19.45 | 11.4 ± 7.3 | 19.9 ± 4.2 | 95.4 ± 37.4 |
| 7j | A, n = 5 | −23.27 | 21.17 | 2.8 ± 0.4 | 14.3 ± 0.3 | 60.1 ± 0.3 |
| 7k | A, n = 6 | 19.38 | 25.53 | 10.5 ± 0.5 | 107.0 ± 24.9 | 305.6 ± 69.3 |
| 7l | B, n = 2 | −30.35 | 37.19 | 2.1 ± 0.9 | 5.4 ± 0.8 | 65.8 ± 28.8 |
| 7m | B, n = 4 | 49.84 | 48.67 | 3.0 ± 1.2 | 4.3 ± 0.1 | 25.0 ± 10.4 |
| 7n | B, n = 5 | 21.64 | 30.39 | 2.1 ± 0.1 | 4.2 ± 0.3 | 33.4 ± 1.6 |
| 7o | B, n = 6 | 69.89 | 94.23 | 7.7 ± 1.8 | 4.2 ± 0.2 | 26.8 ± 9.7 |
| 7p | B, n = 8 | 3.61 | 63.47 | 14.0 ± 4.5 | 4.5 ± 0.0 | 21.8 ± 8.3 |
| 7q | B, n = 10 | 5.33 | 14.25 | 46.4 ± 21.2 | 36.1 ± 0.9 | 70.1 ± 34.3 |
| 7s | B, n = 12 | −7.20 | 45.61 | 57.8 ± 19.5 | 61.0 ± 1.7 | 113.9 ± 29.9 |
| 7t | B, n = 14 | 13.75 | 28.73 | 190.3 ± 26.6 | 363.7 ± 2.4 | 399.4 ± 247.8 |
| GZD824 | – | 2.59 | 20.62 | 1.6 ± 0.7 | 6.8 ± 5.3 | 31.0 ± 11.7 |