Table 1. Dual Sirt2/HDAC6 Inhibitors Tested by Means of Previously Reported Biochemical in Vitro Deacetylation Assays44−46a.
compd | Sirt2 | HDAC6 | Sirt1 | Sirt3 | HDAC1 | HDAC2 | HDAC3 |
---|---|---|---|---|---|---|---|
21 | 11.5 ± 0.04 | 0.15 ± 0.01 | nib | nib | 2.1 ± 0.2 | nte | nte |
22 | 15% @ 10 μM | 0.011 ± 0.001 | nib | nib | 0.21 ± 0.03 | nte | nte |
31 | 0.56 ± 0.27 | 0.025 ± 0.001 | nib | nib | 0.62 ± 0.06 | nte | nte |
32 | 0.15 ± 0.01 | 0.042 ± 0.007 | nib | 17% @ 20 μM | 1.2 ± 0.2 | 1.8 ± 0.1 | 0.71 ± 0.03 |
33 | 0.32 ± 0.11 | 0.043 ± 0.003 | nib | nib | 2.2 ± 0.2 | 6.0 ± 0.2 | 2.5 ± 0.2 |
44 | 0.48 ± 0.04 | 0.0096 ± 0.0003 | nib | nib | 0.60 ± 0.03 | nte | nte |
45 | 0.54 ± 0.01 | 0.017 ± 0.001 | nib | nib | 0.46 ± 0.05 | nte | nte |
46 | 0.48 ± 0.07 | 0.0050 ± 0.0005 | nib | nib | 0.21 ± 0.03 | 0.34 ± 0.02 | 0.14 ± 0.01 |
4 | 0.22 ± 0.01 | 18% @ 10 μM | nib | nib | 10% @ 10 μM | nte | nte |
5 | 0.12 ± 0.01c | nic,d | nic,d | nic,d | nic,d | nte | nte |
55 | nte | 0.65 ± 0.04 | nte | nte | 17 ± 1 | nte | nte |
56 | nte | 0.018 ± 0.001 | nte | nte | 0.81 ± 0.05 | nte | nte |
57 | nie | 0.032 ± 0.004 | nib | nib | 3.2 ± 0.2 | 4.7 ± 0.1 | 4.8 ± 0.4 |
SAHA | nte | 0.030 ± 0.008 | nte | nte | 0.12 ± 0.01 | 0.16 ± 0.01 | 0.11 ± 0.01 |
IC50 values [μM, mean ± SD] or percentual inhibition at a given concentration of the dual Sirt2/HDAC6 inhibitors, as well as reference compounds for selective Sirt2 inhibition (4,5), HDAC6 inhibition (55–57), and SAHA as an nonselective inhibitor of Zn2+-dependent HDACs.
ni = no inhibition (inhibition <15% @ 20 μM).
Values for 5 taken from Vogelmann et al.47
ni = no inhibition (IC50 > 100 μM).
nt = not tested.