Table 2.
Binding Affinities of Selected PBRM1-BD2 Inhibitors Determined by ITC
| ITC Kd (μM)a |
|||||
|---|---|---|---|---|---|
| compd | PBRM1-BD2 | PBRM1-BD5 | SMARCA2B | SMARCA4 | ASH1L |
| 5 | 18.4 ± 3.7 | 179 ± 92 | 15.9 ± 9.7 | ∼142 | NB c |
| 7 | 0.7 ± 0.2 | 0.35 ± 0.04 | 8.1 ± 4.4 | 5.0 ± 0.7 | NB |
| 8 | 6.9 ± 3.1 | 3.3 ± 0.4 | ND b | NB | NB |
| 11 | 9.3 ± 1.1 | 10.1 ± 1.2 | 18.4 ± 9.9 | 69 ± 34 | NB |
| 15 | 5.5 ± 1.0 | 11.1 ± 1.2 | NB | NB | ND |
| 16 | 1.5 ± 0.9 | 3.9 ± 2.6 | NB | NB | ND |
| 34 | 4.4 ± 1.3 | 25 ± 17 | NB | NB | ND |
a
Kd values for each compound were obtained from ITC measurements and calculated by fitting the data points to a sigmoidal curve. The errors were calculated by standard deviation or error of the fit.
b
ND indicates that the value was not determined.
c
NB indicates the compound did not bind to the bromodomain, as demonstrated by generated heat below 0.15 μcal per second in the ITC traces.