Table 2.
Design of BET inhibitors targeting the WPF binding pocket using five-membered aromatic rings
| Compound | BRD4 BD1 | BRD4 BD2 | ||
|---|---|---|---|---|
| IC50 (nM) | Ki (nM) | IC50 (nM) | Ki (nM) | |
| 9 | 2060±420 | 655±269 | 1882±406 | 641±200 |
| 10 | 393±127 | 131±50 | 199±81 | 57.0±17.3 |
| 11 | 155±47 | 44.3±13.9 | 180±37 | 56.4±11.7 |
| 12 | 165±50 | 51.9±18.6 | 108±37 | 30.6±9.0 |
| 13 | 1456±441 | 456±150 | 1139±198 | 335±25 |
| 14 | 102±40 | 41.2±16.9 | 164±44 | 68.7±21.4 |
| 15 | 51.7±15.0 | 19.7±8.2 | 63.5±16.4 | 20.2±9.2 |
| 16 | 40.9±14.2 | 18.5±4.0 | 89.7±18.5 | 31.2±11.8 |
| 17 | 24.1±5.5 | 7.0±3.3 | 11.7±2.0 | 2.7±0.5 |
