Table 1. List of known selective, small molecule inhibitors of PMTs and their mechanism of action (MOA).
Recently discovered inhibitors that are discussed in this review are shown in bold type.
| PMT | Histone targeta |
Non-histone target(s)a |
Inhibitor(s)b [ref] | MOA |
|---|---|---|---|---|
| G9a/GLP | H3K9 | p53 | BIX-01294; UNC0224; E72; UNC0638; BRD4770c; UNC0642; A-366 | Substrate competitive |
| GLP | H3K9 | p53 | MS012 [20] | Substrate competitive |
| EZH2/EZH1 | H3K27 | - | EPZ005687; GSK126; EI1; UNC1999; EPZ-6438; EPZ011989; ZLD1039; CPI-1205 [23]; Compound 1[24] | Co-factor competitive |
| EED-PRC2 | H3K27 | - | A-395 [18]; EED226 [19] | Allosteric/PPI-disruption |
| SETD7 | H3K4 | p53, p65, DNMT1 | PFI-2 | Substrate competitive |
| SMYD3 | H3K4, H4K5 | MAP3K2 | EPZ031686; EPZ030456 | Substrate competitive |
| MENIN-MLL | H3K4 | - | MI-503 | PPI-disruption |
| WDR5-MLL | H3K4 | - | OICR-9429 | PPI-disruption |
| SMYD2 | H3K4, H3K36 | p53, Rb | AZ-505; A-893; LLY507; BAY-598 [32] | Substrate competitive |
| SETD2 | H3K36 | p53 | Pr-SNF | Substrate competitive |
| SETD8 | H4K20 | p53, PCNA | Nahuoic Acid A; UNC0379 [35]; MS2177; MS453 [15] | Substrate competitive |
| SUV420H1/SUV420H2 | H4K20 | - | A-196 [36] | Substrate competitive |
| DOT1L | H3K79 | - | EPZ004777; SGC0946; EPZ-5676, Compounds 2-5 [37–39] | Co-factor competitive |
| PRMT1 | H4R3 | NPL3p, MRE11, 53BP1, ASH2L | AMI-1; NS1; A36; MS023 (Type I PRMT inhibitor) | Substrate competitive |
| PRMT3 | H4R3 | rpS2, PABPN1 | SGC707 | Allosteric |
| CARM1 | H3R17, H3R26 | CBP/p300, PABP, HuR, HuD, CA150, SAP49, SmB, U1C | MS049d [46]; Compound 7 [47]; SGC2085 [48]; TP064 [49] | Substrate competitive |
| PRMT5 | H2AR3, H4R3, H3R2, H3R8 | p53, NF-ββ | EPZ015666; GSK591; LLY-283 [50] | Substrate competitive |
| PRMT6 | H4R3, H3R2 | - | EPZ020411 | Substrate competitive |
a
Histone and non-histone targets of the PMTs (not a comprehensive list). Main targets of the enzymes are shown in bold type.
b
Known inhibitors of PMTs.[9] The inhibitors that are focus of this review are shown in bold type.
c
The inhibitory activity of BRD4770 against GLP was not reported and it was reported to be co-factor competitive.
d
MS049 is a selective, dual CARM1 and PRMT6 inhibitor.