Table 3.
Inhibition and Thermal Shift of Compound 5 Analogues against PBRM1-BD2 as Determined by AlphaScreen and DSF Assaysa,b
| Compound | Structure | IC50 values (μM)a | PBRM1-BD2 ΔTm (°C)a |
|---|---|---|---|
| 5 |
|
4.2 ± 1.3 | 1.0 ± 0.2 |
| 11 |
|
1.0 ± 0.2 | 4.4 ± 0.4 |
| 12 |
|
1.1 ± 0.2 | 3.8 ± 0.4 |
| 13 |
|
1.7 ± 0.3 | 3.3 ± 0.5 |
| 14 |
|
2.1 ± 0.4 | 3.7 ± 0.2 |
| 15 |
|
0.2 ± 0.04 | 5.4 ± 0.1 |
| 16 |
|
0.26 ± 0.04 | 5.4 ± 0.2 |
| 17 |
|
0.87 ± 0.14 | 2.8 ± 0.2 |
| 18 |
|
2.3 ± 0.3 | 3.4 ± 0.3 |
| 19 |
|
50 ± 11 | 1.5 ± 0.8 |
| 20 |
|
5.6 ± 1.0 | 2.9 ± 0.3 |
| 21 |
|
0.86 ± 0.15 | 4.5 ± 0.9 |
| 22 |
|
1.3 ± 0.3b | 5.5 ± 0.3 |
| 23 |
|
>70 | 0.23 ± 0.03 |
| 24 |
|
0.43 ± 0.04 | 5.4 ± 1.2 |
| 25 |
|
0.22 ± 0.02 | 3.9 ± 0.3 |
| 26 |
|
0.29 ± 0.05 | 5.2 ± 0.3 |
| 27 |
|
119 ± 3 | 0.0 |
| 28 |
|
17 ± 4 | 0.3 ± 0.2 |
| 29 |
|
236 ± 38 | 0.0 |
| 30 |
|
89.9 ± 14.8 | 0.0 |
| 31 |
|
>70 | 0.0 |
| 32 |
|
5.6 ± 1.5 | 1.8 ± 0.2 |
| 33 |
|
1.3 ± 0.4 | 2.6 ± 0.3 |
| 34 |
|
0.16 ± 0.02 | 6.4 ± 0.2 |
| 35 |
|
0.29 ± 0.04 | 4.0 ± 0.5 |
a
Values shown are the average of three replicates ± the standard deviation.
b
Compound was partially insoluble at tested concentrations.