Table 1. Enzymatic activity profile of the 8 compounds selected from the virtual screening campaign.
| ID SPECS ID | HeLa % of inhibition at 100 μMa | IC50 (μM)b | |||
|---|---|---|---|---|---|
| HDAC6 | HDAC2 | HDAC8 | HDAC4 | ||
| AK-2 AK-968/40414093 | 10.0 ± 2.0 | 47.9 ± 4.7 | >200 | 140.5 ± 11.5 | >300 |
| AK-5 AK-968/40594025 | 5.8 ± 1.3 | 45.6 ± 1.5 | >200 | 130.0 ± 9.0 | >300 |
| AK-14c AK-968/40468308 | 2.7 ± 1.3 | 12.8 ± 5.4 | >1000 | >300 | >300 |
| AK-18 AK-968/40593432 | 0.4 ± 3.9 | 16.4 ± 1.1 | >1000 | >300 | >300 |
| AK-21 AK-968/41922465 | 14.7 ± 11.6 | 30.9 ± 2.1 | 201.7 ± 1.9 | 74.9 ± 0.8 | >300 |
| AK-24 AK-968/40595505 | 33.3 ± 5.4 | 74.9 ± 5.2 | >200 | 86.9 ± 0.7 | >300 |
| AO-1 AO-080/43441553 | 20.7 ± 4.0 | 16.9 ± 4.9 | >1000 | 35.1 ± 1.1 | 73.5 ± 6.0 |
| AG-1 AG-690/36720038 | 38.2 ± 1.1 | 21.7 ± 1.2 | >1000 | 0.3 ± 0.005 | 110.5 ± 3.5 |
| Trichostatin A | IC50 = 0.0106 ± 0.0027 | 0.0073 ± 0.0007 | 0.0097 ± 0.0009 | 0.41 ± 0.02 | – |
| TMP269 | – | – | – | – | 0.40 ± 0.001 |
aAverage enzyme percentage of inhibition of at least 3 independent experiments in duplicates.
bAverage IC50 of at least 2 independent experiments in duplicates ± SEM.
cPermeability value obtained through PAMPA-BBB assay is Pe = 6.5 ± 0.9 cm/s (CNS +).