Table 2.
The present NNMT inhibitors.
| Type | Name | IC50 | Characteristics | Reference(s) |
|---|---|---|---|---|
| Competitive inhibitors | SAH | 35.3 ± 5.5 μm | Competes with SAM | (47) |
| 1-MNA | 24.6 ± 3.2 μm | Competes with NAM; used in biochemical activity assays | (98) | |
| Sinefungin | 17.0 ± 3.4 μm | A broad-spectrum methyltransferase inhibitor; SAM-dependent | (98) | |
| 5-Amino-1MQ | 1.2 ± 0.1 μm | A low-micromolar inhibition substrate mimetic inhibitor |
(99, 100) | |
| JBSNF-000088 | 0.588 ± 0.075 μm | A small-molecule inhibitor; regulates MNA levels | (19) | |
| Compound 2 | 1.6 μm | A tricyclic compound | (101) | |
| Bisubstrate inhibitors | Compound 78 | 1.41 μm | Incorporates a naphthalene moiety; has a dose-dependent inhibitory effect on cancer cell proliferation | (47) |
| MS2734 | 14 ± 1.5 μm | Noncompetitive with the NAM substrate and competitive with SAM; high selectivity | (102) | |
| Compound 45 | 29.2 ± 4.0 μm | A trivalent compound; the best mimic of the NNMT transition state | (98) | |
| LL320 | 1.6 ± 0.3 nm (Ki) | A reversible, tight-binding inhibitor; the first propargyl-linked bisubstrate analog; poor cell permeability | (103) | |
| NS1 | 0.5 nm (Ki) | The most potent NNMT inhibitor | (104) | |
| Covalent inhibitors | RS004 | 10 μm | Targets the Cys165 residue in the SAM-binding pocket | (105) |
| HS312 | 0.35/0.18 μm | Inhibitory effect correlates negatively with SAM concentrations; engages other protein targets in situ | (106) | |
| Natural product | YD | 0.4 μm | Combines with NNMT interaction and overcomes resistance in NSCLC | (73) |