Table 1.

SAR Profile of P₄ Imidazole-Imine Series

compnd	R1 =	cLogP	Ki (nM) TR-FRETa	Cell Proliferation Assays GI50(nM)a			Selectivityb
			WDR5	MV4:11	MOLM-13	K562	K562/MV4:11
1 c		4.8	<0.02	38 ± 9.0	78 ± 13	8000 ± 4100	210
2		4.0	0.033 ± 0.005	210 ± 19	420 ± 30	18000 ± 2800	86
3		3.7	0.035 ± 0.005	88 ± 20	220 ± 23	>30000	>340
4		3.2	0.036 ± 0.005	1200 ± 310	3900 ± 410	>30000	>25
5		2.7	0.055 ± 0.005	560 ± 84	1600 ± 200	>30000	>54
6		3.7	0.022 ± 0.001	640 ± 120	2400 ± 240	>30000	>47
7		3.9	<0.02	120 ± 59	290 ± 170	>29000	>240
8		3.2	0.029 ± 0.002	230 ± 52	640 ± 120	>30000	>130
9		3.7	<0.02	200 ± 52	560 ± 76	>30000	>150
10		2.4	0.046 ± 0.002	850 ± 240	2100 ± 410	>30000	>35
11		2.6	0.023 ± 0.001	210 ± 49	570 ± 85	>30000	>140
12		2.5	0.21 ± 0.008	19000 ± 3000	>30000	>30000	>2
13		3.1	0.025 ± 0.003	85 ± 17	270 ± 31	>30000	>350
14		3.5	<0.02	39 ± 9.0	110 ± 7.8	>30000	>770
15		4.0	<0.02	36 ± 11	110 ± 9.8	>30000	>830

^aTR-FRET K_i, and cell proliferation GI₅₀ values represent four independent replicate determinations ± standard deviation.

^bSelectivity is defined a GI_50,K562/GI_50,MV4:11 and is used to generally distinguish between on- and off-target inhibition mechanisms.

^cThe data for 1 were reported in our previous report.³⁵