Table 3.
Results of in vitro FRET-based screening using reporter compound 17 of the inhibition of lipase activities
| Compound Number | Detail of N-formyl- α-amino ester | hDAGLα inhibition at 10 μM detergent free or (0.05% Triton X-100) (%) | Lipoprotein Lipase (Bacterial) inhibition at 10 μM (%) | Pancreatic Lipase (Porcine) inhibition at 10 μM (%) | ||
|---|---|---|---|---|---|---|
| 3 (THL) | L-leucyl | 92, | 86* | (99) | 92 | 98 |
| 4 (OMDM-188) | L-isoleucyl | 92 | (99) | 84 | 99 | |
| 5 | L-allo-isoleucyl | 92 | (99) | 61 | 98 | |
| 6 | D-isoleucylA | 90 | (98) | 86 | 99 | |
| 7 | D-allo-isoleucyl | 90 | (98) | 68 | 95 | |
| 8 | (S)-α-aminobutyryl | 93 | (100) | 80 | 97 | |
| 9 | none | 14 | (72) | <0 | 38 | |
| trans-10 | none | 69* | 67 | 96 | ||
| cis-11 | none | 65* | 33 | 94 | ||
| JZL184 | NA | 59, | 44* | 36 | 36 | |
| URB597 | NA | 22, | 7* | 21 | 68 | |
| n-C16H33SO2F | NA | 40, | 94* | 8 | 29 | |
| PMSF | NA | 8* | <0 | 17 | ||
| RHC80267 (1) | NA | 70, | 40* | <0 | 78 | |
| SD41 | NA | 17, | 7* | <0 | <0 | |
| JZL195 | NA | 84, | 55* | <0 | 43 | |
NA, not applicable
A
5% impurity in D-isoleucyl analog due to D-allo-isoleucyl analog
*
protein was pretreated with JZL184 to completely inhibit MAGL activity