Table 2.
Overview of known MAGL inhibitors classified as chemotype and assay type.
| Chemotype | Inhibitor | Reversibility | MAGL inhibition (IC50 nmol/L) |
||
|---|---|---|---|---|---|
| Surrogate substrate assay | Natural substrate assay | ABPP assay | |||
| Maleimides | NAM (2) | Irreversible | 112080 (hMAGL) | ||
| Disulfides | Disulfiram (4) | Irreversible | 36081 (hMAGL) | ||
| Compound 6 | Irreversible | 16681 (hMAGL) | |||
| Carbamates | URB602 (7) | Partially reversible | 1000080 (hMAGL) 2800082 (rMAGL) |
||
| JZL184 (8) | Irreversible | 48068 (hMAGL) | 89 (mMGAL) 9583 (mMAGL) 270083 (rMAGL) 69 (hMAGL) |
1084 (mMGAL) 26284 (rMAGL) 3.984 (hMAGL) |
|
| KML29 (9) | Irreversible | 2.584 (mMAGL) 0.8583 (mMAGL) 2.583 (rMAGL) 3.683 (hMAGL) |
1584 (mMAGL) 4384 (rMAGL) 5.984 (hMAGL) |
||
| JW651 (10) | Irreversible | 4.575 (mMAGL) | 3875 (mMAGL) | ||
| MJN110 (11) | Irreversible | 2.185 (mMAGL) | 9.575 (mMAGL) | ||
| SAR127303 (14) | Irreversible | 4868 (hMAGL) | |||
| PF06795071(20) | Irreversible | 386 (hMAGL) | |||
| ABX-1431 (21) | Irreversible | 876 (hMAGL) 2176 (hMAGL, brain cortex) 1476 (hMAGL, PC3 cells) 2776 (mMAGL) 2676 (rMAGL) |
|||
| Ureas | SAR629 (22) | Irreversible | 0.2283 (mMAGL) 1.183 (rMAGL) |
||
| ML30 (23) | Irreversible | 0.5487 (hMAGL) | 1.983 (mMAGL) 4.483 (rMAGL) 1.583 (hMAGL) |
||
| JJKK-048 (25) | Irreversible | 0.2883 (mMAGL) 0.2483 (rMAGL) 0.3683 (hMAGL) |
|||
| Arylthioamides | CK37 (30) | Irreversible | 15488 (hMAGL) | ||
| THL-based | OMDM169 (31) | Partial reversible (covalently) | 7.389 (mMAGL) 0.3489 (rMAGL) 89089 (hMAGL) |
||
| Natural terpenoids | Pristimerin (35) | Reversible | 9390 (rMAGL) | ||
| Euphol (36) | Reversible | 31590 (rMAGL) | |||
| Isothiazolines | Octhilinone (32) | Partial reversible | 8834 (rMAGL) | ||
| Others | Compound 41 | Reversible | 18091 (mMAGL) 24091 (rMAGL) |
||
| Compound 43 | Reversible | 84092 (hMAGL) | |||
| Compound 44 | Reversible | 8093 (hMAGL) | |||
| Compound (R)-49 | Reversible | 3.670 (hMAGL) | |||
Note: mMAGL, mouse brain MAGL; rMAGL, rat brain MAGL; hMAGL, human recombinant MAGL.