Table 1. SAR, biological and computational results of the BIX-01294 derivatives ^a .

Compound ID	Scaffold	R2	Activity% compound b (μM)			IC50 c (μM)	c log P d	N-1 pK a e	Docking score (kcal mol–1)
			50	10	1				SP	XP
1 (BIX-01294)			6	6	11	0.067 ± 0.003	3.9	8.13 (±2.22)	–7.859	na
2 (HKMTI-1-005)			5	6	19	0.101 ± 0.010	3.5	5.60 (±2.22)	–6.995	–6.380
3 (HKMTI-1-022)			7	9	35	0.472 ± 0.017	4.7	7.47 (±1.47)	–5.789	–4.244
4 (HKMTI-1-011)			15	31	79	3.190 ± 0.080	4.4	8.10 (±1.47)	na	na
12			99	102	99	—	2.9	4.57 (±0.70)	na	na
13			98	100	107	—	2.5	4.66 (±0.70)	na	na
14			97	96	101	—	3.7	5.31 (±0.70)	na	na
15			102	98	107	—	3.4	5.77 (±0.70)	na	na
16			47	82	91	—	3.9	5.68 (±0.70)	na	na
17			62	83	105	—	3.5	5.77 (±0.70)	na	na
18			91	102	114	—	4.8	6.42 (±0.70)	na	na
19			104	105	98	—	4.5	6.88 (±0.70)	na	na
20			81	96	91	—	3.9	3.28 (±2.22)	na	na
21			88	92	105	—	3.5	3.35 (±2.22)	na	na
22			93	105	105	—	4.8	3.86 (±2.22)	na	na
23			67	90	101	—	2.6	3.15 (±2.22)	na	na
24			101	90	97	—	3.4	3.73 (±2.22)	na	na
25			55	84	96	—	3.2	6.62 (±0.70)	na	na
31			63	91	98	—	3.2	5.58 (±2.22)	na	na
32			78	95	96	—	4.4	7.45 (±1.47)	na	na
33			109	98	96	—	4.2	8.08 (±1.47)	na	na
34			18	46	93	—	3.8	8.06 (±2.22)	na	na
35			27	59	94	—	3.5	5.53 (±2.22)	na	na
36			72	82	94	—	4.7	7.40 (±2.22)	na	na
37			97	108	104	—	4.4	8.03 (±2.22)	na	na
41 (HKMTI-1-248)			5	4	6	0.013 ± 0.001	4.5	10.57 (±2.22)	–7.522	–6.904
42 (HKMTI-1-247)			5	6	7	0.031 ± 0.003	4.1	9.84 (±2.22)	na	–6.476

^aR₁ is the same for all compounds: R₁ = , SP = standard precision mode, XP = extra precision mode, na = no desired pose found.

^bThe experiment was conducted in duplicate.

^cThe assay was conducted in triplicate at K _m of both substrates (0.8 μM peptide [H3 1–25] and 8 μM SAM) for G9a (5 nM).¹⁷

^d c log P values were calculated using the freely available program RDkit.³⁴

^e‘Sequential’ pK _a values were calculated at pH 7.0, with water as the solvent model, using the Epik 2.7 program implemented in Schrodinger (see ESI).