TABLE 1.
In vitro anti-HIV-1 activity (EC50), cytotoxicity (CC50), and in vitro metabolic stabilities of tenofovir and tenofovir prodrugs
| Prodrug | EC50a (μM) | CC50a (μM)b | Selectivity indexb |
t1/2 (min)b
|
|
|---|---|---|---|---|---|
| MT-2 cell extract | Human plasma | ||||
| Tenofovir | 5.0 ± 2.6 | 6,000 ± 2,700 | 1,250 | NR | NR |
| Tenofovir DF | 0.05 ± 0.03 | 50 ± 28 | 1,000 | 70.7 ± 10.1 | 0.41 ± 0.20 |
| GS 7171 | 0.01 ± 0.005 | 95 ± 37 | 9,500 | ND | ND |
| GS 7339 | 0.06 ± 0.04 | >100 | >1,700 | >1,000 | 231 ± 72 |
| GS 7340 | 0.005 ± 0.002 | 40 ± 29 | 8,000 | 28.3 ± 7.4 | 90 ± 12 |
| GS 7485 (d-Ala) | 10 ± 4 | ND | ND | >700 | >200 |
| GS 7160 | 10 ± 2.5 | ND | ND | ND | ND |
a
The data represent means ± SD from two to four independent determinations.
b
NR, not reactive; ND, not determined.