. 2021 Jun 25;10(7):581. doi: 10.3390/biology10070581

Table 2.

Potential therapeutic inhibitors targeting H3K4-specific HMTs.

Inhibitor	Mode of Action	Kd or Ki	Methylation IC₅₀	PPI IC₅₀	GI₅₀	Cancer Cell Type	In Vivo Validation	Ref
MM-102	WDR5–MLL	<1 nM	400 nM	2.4 nM	25 μM	MLL1-rearranged leukemia		[200]
MM-401	WDR5–MLL	<1 nM	320 nM	0.9 nM	5.9~12.6 μM	MLL1-rearranged leukemia		[201]
MM-589	WDR5–MLL	<1 nM	12.7 nM	0.9 nM	0.21~0.25 μM	MLL1-rearranged leukemia		[202]
WDR5-0103	WDR5–MLL	450 nM	39 μM					[203]
OICR-9429	WDR5–MLL	30 nM			~5 μM	C/EBPα-mutant AML Ovarian cancer (with topotecan) Prostate cancer (with cisplatin)	Yes Yes	[204,207] [208] [209]
Piribedil	WDR5–MLL		180 nM		65~92 μM	MLL1-rearranged AML	Yes	[205]
Win6mer	WDR5–MLLWDR5–SETD1A	2.9 nM	2.2 nM2.5 nM					[206]
Compound C6	WDR5–MLL	0.1 nM	20 nM		2.5~6.4 μM	MLL1-rearranged leukemia		[210]
Compound 16	WDR5–MLL	<0.02 nM	2.2 nM		38~78 nM 0.26~0.49 μM	MLL1-rearranged leukemia Neuroblastoma and Burkitt’s lymphoma		[211]
MCP-1	Menin–MLL	4.7 nM		18.5 nM		MLL1-rearranged leukemia		[212]
MI-2	Menin–MLL	158 nM		446 nM	7.2~18 μM	MLL1-rearranged leukemia		[213]
MI-2-2	Menin–MLL	22 nM		46 nM	3 μM	MLL1-rearranged leukemia (with DOT1L inhibitor)	Yes	[214,215]
MI-463	Menin–MLL	9.9 nM		15.3 nM	0.23 μM	MLL1-rearranged leukemia	Yes	[216]
MI-503	Menin–MLL	9.3 nM		14.7 nM	0.22 μM 1.5~11.7 μM	MLL1-rearranged leukemia Castration-resistant prostate cancer	Yes Yes	[216] [135]
MI-538	Menin–MLL	6.5 nM		21 nM	83 nM	MLL1-rearranged leukemia	Yes	[217]
MI-3454	Menin–MLL			0.51 nM	7.6~27.1 nM	MLL1-rearranged or NPM1-mutated leukemia	Yes	[218]
BAY-155	Menin–MLL	75 nM		8 nM	90~140 nM	MLL1-rearranged leukemia	Yes	[219]
VTP50469	Menin–MLL	104 pM			13~37 nM	MLL1-rearranged leukemia	Yes	[220]
M-89	Menin–MLL	1.4 nM		5 nM	25~55 nM	MLL1-rearranged leukemia		[221]
M-525	Menin–MLL			3.3 nM	2.3~10.3 nM	The first irreversible Menin inhibitor		[222]
M-808	Menin–MLL			2.6 nM	1~4 nM	MLL1-rearranged leukemia	Yes	[223]
AZ505	SMYD2	500 nM	120 nM			MDR-clear cell renal cell carcinoma (ccRCC) Triple-negative breast cancer	Yes	[224] [117]
LLY-507	SMYD2		<15 nM		1.5~6 μM 1.77~2.9 μM	Esophageal, liver, and breast cancer cells High-grade serous ovarian carcinomas (HGSOCs).		[225] [226]
A-893.	SMYD2		2.8 nM			Lung cancer		[227]
BAY598	SMYD2	1.1~1.2 nM	27 nM		<10 μM	Esophageal cancer (combi w/doxorubicin)	Yes	[228]
EPZ031686	SMYD3	1.3~4.7 nM	3 nM					[229]
EPZ028862	SMYD3		1.8 nM		>40 μM	Esophageal squamous cell carcinoma		[230]
GSK2807	SMYD3	14 nM	130 nM					[231]
Compound 29	SMYD3	440 nM	11.7 nM		17.7 μM (2D) 1.04 μM (3D)	Hepatocarcinoma		[232]
(R)-PFI-2	SETD7/9	0.33 nM	2 nM			Breast cancer cells		[233]