Table 1.

IC₅₀ values of 1 and analogues against BRD4 D1 by fluorescence anisotropy and AlphaScreen. Kinase activity against p38α.

Cpd	R =	R1 =	BRD4 D1 IC50 by FAa(μM)	BRD4 D1 IC50 by AlphaScreenb(μM)	p38α Kdc(nM)
(+)-JQ1	-	-	0.037 ± 0.008	0.051 ± 0.02†	-
1	F	H	11 ± 0.8	3.8	0.47
2	H	H	4.5 ± 0.2	2.6	-
3	CH3	H	1.2 ± 0.2	1.1	-
4	CF3	H	0.31 ± 0.06	0.64	260
5	CF3	(CH2)2NH2	0.13 ± 0.01	0.29	1900
6	CF3	(CH2)2N(CH3)2	0.15 ± 0.03	0.20	-
7	CF3	(CH2)2NHCOCH3	0.42 ± 0.01	1.5	-
8	CF3	(CH2)2NH2	1.1 ± 0.2	1.3	>30,000

^aData represents the mean and standard deviation of three biological replicates.

^bData represents the mean of two technical replicates except (+)-JQ1.

^†Data represents the mean and standard deviation of six biological replicates.

^cK_d values were determined by KINOMEscan. Data represents the mean of two biological replicates.