Table 1.

SAR Profile of Substituted Benzamide WDR5 WIN site inhibitors

compnd	R1 =	Kd (nM) TR-FRET	HMT IC50 (nM)	Cell Proliferation Assays GI50 (nM)			Selectivity
		WDR5	MLL1	MV4:11	Molml3	K562	K562/MV4:11
2		1.5 ±0.80	43.3	2300 ± 620	2000 ± 230	13000 ± 3000	5
3		0.50 ±0.010	55.0	2400 ± 660	2700 ± 440	18000 ±6300	7
4		0.14 ±0.065	14.0	870 ± 320	840 ± 93	6400 ±1400	7
5		0.16 ±0.026	9.9	820 ± 400	970 ± 400	15000 ±850	18
6		16 ± 14	>3000	13000±1300	7600 ± 460	28000 ± 2400	2
7		0.030 ±0.014	3.4	390 ±150	390 ± 52	3600 ±1100	9
8		0.090 ± 0.002	28.4	1300±190	1500 ±220	10000 ± 3400	8
9		0.032 ± 0.005	11.6	360 ± 200	405 ± 83	7600±1500	21
10		0.035 ± 0.002	8.6	240 ± 28	300 ± 49	12000 ± 3800	50
11		0.055 ± 0.021	23.9	340 ± 86	510 ±140	5900 ±1200	17
12		0.061 ± 0.023	3.4	490 ± 25	580 ±170	4900 ± 940	10
13		0.049 ± 0.008	3.4	470 ± 25	480 ±110	15000 ± 3600	32

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

^bHistone methyltransferase inhibition (HMT) IC₅₀ values represent two independent replicate determinations.

^cSelectivity is defined as GI_{50, K562}/GI_{50, MV4:11}.