Table 2.
Metabolic stability, Cytotoxicity, and On-target activity of selected compounds.
| Compda | T1/2 HLM (min)b | HepG2 cytotoxicityc | Gwt1 Overexpression ratiod | PigW Inhibitione |
|---|---|---|---|---|
| MGX | 49.9 | 98 | 8 | 0 |
| 8d | 3.15 | - | - | - |
| 8e | 14.4 | - | - | - |
| 12a | 43.0 | 93 | 16 | 0 |
| 12b | 61.5 | 77 | - | - |
| 12d | 17.3 | - | - | - |
| 13a | 62.3 | 97 | 8 | 5 |
| 13b | 93.9 | 102 | 8 | 0 |
| 13c | 37.1 | - | - | - |
| 13i | 4.65 | - | - | - |
| 13l | 68.2 | 98 | 4 | 80 |
| 13m | 20.3 | - | - | - |
a
Italicized compound numbers indicate a compound that has been previously synthesized by Eisai. MGX, manogepix. Values were determined according to the methods for
b
under b) HLM half-life, for
c
under c) Cytotoxicity assay (% viability at 3 μM)), for
d
under d) Overexpression assay and for
e
under e) PigW assay (% inhibition at 16 μM). Values in bold fulfill the selection criteria.