Table 6.
compd | R3 | stereocenter | BRD4 D1 IC50 by FA (μM)a | % Inhibition against BRD2 D1 at 50 μMa | % Inhibition against BRDT D1 at 50 μMa |
---|---|---|---|---|---|
(+)-JQ1 | <0.092b | 0.14 ± 0.001c | 0.12 ± 0.04c | ||
23 | H | 0.36 ± 0.03 | 79% | 68% | |
24 | (CH2)2N(CH3)2 | <0.092b | 88% | 88% | |
25 | H | 0.30 ± 0.01 | 84% | 73% | |
26 | (CH2)2N(CH3)2 | <0.092b | 89% | 85% | |
27 | H | S | 1.1 ± 0.3 | 49% | 49% |
28 | (CH2)2N(CH3)2 | S | 0.11 ± 0.02 | 73% | 70% |
29 | H | S | 0.88 ± 0.2 | 57% | 54% |
30 | (CH2)2N(CH3)2 | S | <0.092b | 87% | 88% |
31 | H | R | 3.8 ± 0.5 | 41% | 46% |
32 | (CH2)2N(CH3)2 | R | 0.44 ± 0.08 | 59% | 72% |
Data represents the mean and standard deviation of three experimental replicates.
IC50 is less than half the concentration of bound BRD4 D1 used.
IC50 values by fluorescent anisotropy.