TABLE 1.
In vitro activity against HDAC1, cytotoxicity in Jurkat cells, and reactivation of latent HIV-1 in J89GFP cells by structurally diverse HDACI
| HDACI | IC50 against HDAC1 | Cytotoxicity CC50 | Reactivation dosea | % inhibition of HDAC1 at reactivation doseb | % EGFP-positive J89GFP cells (after 24 h) |
|---|---|---|---|---|---|
| μm | μm | μm | |||
| HC toxin | 0.000154 | 0.05 | 0.005 | 99.7 | 1.3 |
| Apicidin | 0.000299 | 10.0 | 0.5 | 99.7 | 40.6 |
| Oxamflatin | 0.003959 | 6.0 | 0.5 | 99.2 | 31.2 |
| Scriptaid | 0.006421 | 6.0 | 0.5 | 98.7 | 3.2 |
| SAHA | 0.0137 | 10.0 | 0.5 | 97.3 | 2.5 |
| TSA | 0.0169 | 0.10 | 0.05 | 74.7 | 17.2 |
| M344 | 0.0941 | 0.5 | 0.1 | 51.5 | 3.1 |
| CAY10398 | 1.7780 | 1.0 | 0.5 | 21.9 | 0.9 |
| MC1293 | 4.245 | 10.0 | 5 | 54.1 | 2.7 |
| CAY10433 | 9.36 | 1000 | 10 | 51.6 | 5.2 |
| SBHA | 4.54 | 100 | 100 | 95.6 | 57.5 |
| Depudecin | 25.33 | 5.0 | 1 | 3.8 | 1.3 |
| Sodium 1-naphthoate | 200.6 | 10 | 10 | 4.75 | 1 |
| Valproic acid | 171 | 10,000 | 1000 | 85.4 | 4.3 |
| Sodium butyrate | 175 | >10,000 | 1000 | 85.1 | 66.4 |
| Sodium 4-phenylbutyrate | 162 | 10,000 | 1000 | 86.1 | 2.5 |
a The highest nontoxic concentration of HDACI (determined from the cytotoxicity assays in Jurkat cells) was administered to the J89GFP cells to determine the inhibitor's ability to reactivate latent HIV-1.
b Maximum possible inhibition of HDAC1 at the concentration of inhibitor used in the reactivation experiments in J89GFP cells is shown (the actual inhibition in the J89GFP cells is likely to be significantly less due to inefficient cellular uptake and nonspecific protein binding).