Table 1.
DSF thermal shift (°C stabilization, 10 μM compound) SAR for Family VIII bromodomains. Values are derived from at least three determinations with standard deviations quoted.
| Structure | PB1(2) | PB1(3) | PB1(4) | PB1(5) | SMARCA2A | SMARCA2B | SMARCA4 | |
|---|---|---|---|---|---|---|---|---|
| 2 |
|
2.0±0.2 | 0.5±0.1 | 0.7±0.2 | 4.9±0.6 | 4.8±0.4 | 2.0±0.2 | 3.3±0.2 |
| 3 |
|
4.1±0.3 | 1.7±0.1 | 1.2±0.2 | 7.8±0.7 | 7.8±0.1 | 4.8±0.2 | 7.0±0.3 |
| 4 |
|
3.2±1.9 | 1.8±0.5 | 1.0±0.2 | 6.9±0.7 | 8.2±0.7 | 3.9±0.2 | 6.3±0.6 |
| 5 |
|
0.9±0.2 | 0.7±0.0 | 1.3±0.1 | 7.0±0.3 | 7.4±0.1 | 3.7±0.2 | 7.5±0.1 |
| 6 |
|
5.2±0.6 | 3.3±0.1 | 2.0±0.4 | 6.6±0.4 | 5.1±0.4 | 2.0±0.1 | 3.8±0.5 |
| 7 |
|
0.7±0.9 | 0.3±0.2 | 0.6±0.2 | 4.6±1.3 | 2.9±0.7 | 1.1±0.6 | 2.9±1.2 |
| 8 |
|
2.5±0.4 | 1.1±0.2 | 0.4±0.1 | 8.3 ±0.4 | 5.4±0.1 | 2.4±0.4 | 6.1±0.4 |
| 9 |
|
2.3±0.2 | 1.1±0.1 | 0.7±0.2 | 5.7±0.4 | 5.5±0.2 | 3.0±0.1 | 4.7±0.1 |
| 10 |
|
0.1±0.2 | 0.0±0.0 | 0.3±0.4 | 0.4±0.5 | 0.7±0.2 | −0.4±0.1 | 0.7±0.1 |
| 11 |
|
6.7±0.3 | 3.5±0.1 | 2.4±0.2 | 9.1±0.8 | 10.1±0.5 | 5.0±0.1 | 7.7±0.2 |
| 12 |
|
4.6±0.4 | 1.9±0.2 | 1.6±0.0 | 8.0±0.3 | 5.8±0.2 | 3.0±0.4 | 5.3±0.4 |
| 13 |
|
3.5±0.4 | 1.3±0.1 | 1.2±0.2 | 5.1±0.8 | 4.1±0.4 | 2.2±0.3 | 3.4±0.2 |
| 14 |
|
3.8±1.2 | 1.5±0.1 | 1.2±0.1 | 8.0±0.8 | 5.9±0.2 | 3.8±0.3 | 5.8±0.7 |
| 15 |
|
2.2±0.2 | 0.9±0.0 | 0.6±0.1 | 7.6±0.6 | 7.5±0.7 | 4.1±0.4 | 6.1±0.3 |
| 16 |
|
1.4±0.0 | 0.6±0.0 | 0.4±0.1 | 9.1±0.9 | 8.2±0.4 | 5.0±0.2 | 7.0±0.2 |
| 17 |
|
5.9±0.3 | 6.4±0.2 | 2.1±0.4 | 9.3±0.7 | 8.5±0.7 | NT | 7.4±0.7 |
| 18 |
|
NT | NT | NT | −0.4±0.3 | 0.7±0.3 | −0.4±0.2 | 0.7±0.3 |