TABLE 2.
In vitro activity profiles of lipid prodrugs of TFV featuring increasing distances between phosphorus and oxygen. All HIV and cytotoxicity results compounds formulated as HSA complexes in 5: 1 M ratios. Nd = not determined.
| Compound ID | Lipid motif (R) | Linear atom # | HLM t1/2 (min) | HIV IC50 (µM) | St. Dev. (µM) | CC50(µM) | St. Dev. (µM) | Therapeutic index | |
|---|---|---|---|---|---|---|---|---|---|
| 18 |
|
20 | 35 | 0.003 | 0.001 | 69.6 | 1.31 | 23,200 |
|
| TXL |
|
20 | 42 | 0.018 | 0.010 | 97.6a | 2.68 | 5,420 | |
| 19 |
|
20 | 48 | 0.030 | 0.014 | >100a | — | >3,330 | |
| 20 |
|
20 | 31 | 0.052 | 0.03 | >100b | — | >1,920 |