Table 1.
Inhibition of XMRV protease by approved anti-HIV drugs (top 6 compounds) and by other protease inhibitors designed against retroviral proteases and malarial aspartic proteinases.
| Inhibitor | aKi | bKi |
|---|---|---|
| nM | ||
| Amprenavir | 0.2 | 10 ± 2.0 |
| Atazanavir | 1.8 | 22 ± 1.4 |
| Darunavir | n.d. | 15 ± 0.7 |
| Tipranavir | n.d. | 27 ± 2.1 |
| Lopinavir | n.d. | 32 ± 3.5 |
| Ritonavir | n.d. | 36 ± 4.2 |
| TL-3 | 102 | n.d. |
| Pepstatin A | 1442 | n.d. |
| DMP 323 | n.d. | 18 ± 1.4 |
| 132830c | n.d. | 97 ± 8.5 |
| 129463c | n.d. | 63 ± 2.8 |
| 14d | n.d. | 26 ± 3.5 |
| 2d | n.d. | 202 ± 36.1 |
| 1d | n.d. | 329 ± 21.2 |
| 3d | n.d. | 333 ± 35 |
a
Ki determined by assay with oligopeptide substrate RSLLY↓PALTP using an HPLC-based method at 37 °C.
b
Ki determined by assay with chromogenic substrate KARVnL↓NphEAnLG at 25 °C.
c
Compounds 132830 and 129463 were identified by virtual screening of the XMRV PR active site against the library of the Developmental Therapeutics Program of NCI/NIH.
d
Compound numbers from Table 1 of ref. [51].