Table 1.
Structure of pyridine-2-carboxylic acid inhibitors and their inhibition of HsMetAP1, HsMetAP2, and cell proliferations
| Compound |  |
IC50, μM |
Ratio |
IC50, μM |
||
|---|---|---|---|---|---|---|
| R | hMetAP1 | hMetAP2 | MetAP1/MetAP2 | HeLa | HT1080 | |
| 1 |  |
1.5 ± 0.2 | >300 | <0.005 | 0.6 ± 0.1 | 0.3 ± 0.1 |
| 2 |  |
2.9 ± 0.1 | >500 | <0.006 | 3.9 ± 0.2 | 2.5 ± 0.3 |
| 3 |  |
3.5 ± 0.2 | >500 | <0.007 | 5.1 ± 0.3 | 4.3 ± 0.1 |
| 4 |  |
6.4 ± 0.6 | >1,000 | <0.006 | 8.9 ± 0.5 | 9.5 ± 0.8 |
| 5 |  |
>500 | >500 | N.A. | >50 | >50 |
Results from cobalt (II) supplied enzymatic assay are shown. Each experiment was conducted in triplicate. N.A., not applicable.