Table 2.
Comparison of DAPN-PD, IDX-184 and BMS-986094 intracellular metabolism in Huh-7 and HepG2 cells.
| Compounda | Cell type | Intracellular concentration of prodrugs and metabolites (pmol/106 cells ± SD)b | ||||
|---|---|---|---|---|---|---|
| Prodrugs | Nc | 2’-C-Me-G | NTPc | 2’-C-Me-GTP | ||
| DAPN-PD | Huh-7 | 170 ± 4 | 47 ± 3 | 7.5 ± 1.5 | 0.55 ± 0.11 | 2.0 ± 0.1 |
| HepG2 | 390 ± 33 | 27 ± 2 | 90 ± 12 | 1.2 ± 0.01 | 2.8 ± 0.4 | |
| IDX-184 | Huh-7 | 11 ± 1 | NA | 5.6 ± 1.6 | NA | 3.1 ± 0.3 |
| HepG2 | 21 ± 1 | NA | 20 ± 1 | NA | 2.1 ± 0.4 | |
| BMS-986094 | Huh-7 | 2,900 ± 358 | 220 ± 18 | 640 ± 36 | 0.32 ± 0.04 | 240 ± 13 |
| HepG2 | 2,400 ± 9 | 220 ± 1 | 4,900 ± 108 | 0.57 ± 0.10 | 350 ± 7 | |
a
Cells were incubated with each compound for 4 h at 50 μM.
b
Values represent the mean ± SD of three replicates.
c
For DAPN-PD, N is 2’-C-Me-DAPN; for BMS-986094, N is 2’-C-Me-6-OMe-G.
NA is not applicable.