Results from NanoBRET assays. IC50 values (mean ± SD) and calculated Ki values based on the Cheng–Prusoff equationa of our Sirt2 inhibitors and different published Sirt2 inhibitors. n.i. = no inhibition (% inhibition < 10%@100 μM).
| Compound | In vitro Sirt2 activity assay | NanoBRET assay | Compound | In vitro Sirt2 activity assay | NanoBRET assay | ||
|---|---|---|---|---|---|---|---|
| IC50 [μM] | IC50 [μM] | K i value [μM] | IC50 [μM] (ref) | IC50 [μM] | K i value [μM] | ||
| SirReal2 | 0.44 ± 0.08 | 43%@10 μM | — | AEM2 | 3.8 (70) | 5.2 ± 0.2 | 0.58 ± 0.02 |
| 2 | 0.12 ± 0.01 | 2.7 ± 0.1 | 0.30 ± 0.01 | AK-7 | 15.5 (71) | 20 ± 1.6 | 2.3 ± 0.2 |
| 7 | 624 ± 71.9 | n.i. | — | EX-527 | 32.6 (72) | n.i. | — |
| 8 | 0.16 ± 0.02 | 1.0 ± 0.05 | 0.11 ± 0.005 | JH-T4 | 0.29 ± 0.01 | 1.9 ± 0.2 | 0.28 ± 0.06 |
| 9 | 0.17 ± 0.02 | 0.40 ± 0.02 | 0.04 ± 0.002 | Ro 31-8220 | 0.8 (73) | 9.9 ± 0.6 | 1.1 ± 0.07 |
| 10 | 0.15 ± 0.01 | 0.41 ± 0.02 | 0.05 ± 0.002 | Sirtinol | 38–58 (72) | n.i. | — |
| 11 | 0.11 ± 0.005 | 37%@10 μM | — | ||||
| 12 | 0.12 ± 0.01 | 0.098 ± 0.004 | 0.01 ± 0.005 | ||||
a
For the calculation we used the tracer concentration in the medium as this is a common procedure in literature.74–76