TABLE 1.
List of known sirtuin modulators.
| Compound | The biological effect in NDD | Enzyme activity | Target/Specificity | References |
|---|---|---|---|---|
| Resveratrol | AD, PD, HD | SIRT1 EC1.5 = 46.2 μM | SIRT1 activator | Borra et al. (2005), Milne et al. (2007), Rocha-González et al. (2008), Turner et al. (2015) |
| Piceatannol | AD | — | SIRT1 activator | Kim et al. (2008) |
| SRT1720 (paeonol) | HD | SIRT1 EC50 = 0.16 μM | SIRT1 activator | Milne et al. (2007) |
| SRT2104 | HD | — | SIRT1 activator | Libri et al. (2012), Jiang et al. (2014) |
| Nicotinamide (NAM) | AD, PD, HD | SIRT1 IC50 = 1.2 μM SIRT2 IC50 = 85 μM | Inhibitor- SIRT1-7 | Avalos et al. (2005), Hathorn et al. (2011), Di Fruscia et al. (2015) |
| Sirtinol | — | ySir2 IC50 = 70 μM SIRT1 IC50 = 131 μM SIRT2 IC50 = 49 μM | Inhibitor- SIRT1 and 2 | Shin et al. (2013), Li et al. (2014) |
| EX527/Selisistat | HD | SIRT1 IC50 = 0.098 μM SIRT2 IC50 = 19.6 μM | SIRT1 inhibitor | Napper et al. (2007), Süssmuth et al. (2015) |
| CHIC35 | — | SIRT1 IC50 = 0.124 μM SIRT2 IC50 = 2.77 μM | Inhibitor SIRT1 and 2 | Napper et al. (2007) |
| Cambinol | AD | SIRT1 IC50 = 56 μM SIRT2 IC50 = 59 μM | Inhibitor- SIRT1 and 2 | Bilousova et al. (2018), Chowdhury et al. (2020) |
| Splitomicin | — | ySir2 IC50 = 60 μM SIRT1: No inhibition >500 μM | Inhibitor ySir2 | Carafa et al. (2016) |
| Tenovin-1 | — | IC50s not determined due to lack of water solubility | Inhibitor- SIRT1 and 2 | Lain et al. (2008) |
| Tenovin-6 | — | SIRT1 IC50 = 21 μM SIRT2 IC50 = 10 μM | Inhibitor- SIRT1, 2 and 3 | Carafa et al. (2016) |
| Suramin | — | SIRT1 IC50 = 0.29 μM SIRT2 IC50 = 1.2 μM SIRT5 IC50 = 22 μM | Inhibitor- SIRT1,2 and 5 | Schuetz et al. (2007), Trapp et al. (2007) |
| AK1/7 | HD, PD | SIRT2 IC50 = 15.5 μM SIRT1/3 no inhibition >50 μM | SIRT2 inhibitor | Spires-Jones et al. (2012), Chen et al. (2015), Di Fruscia et al. (2015) |
| β-Lapachone | HD | — | SIRT1 activator | Shin et al. (2013), Lee et al. (2018) |
| AGK2 | PD, HD | SIRT1 IC50 > 50 μM SIRT2 IC50 = 3.5 μM | SIRT2 inhibitor | Rumpf et al. (2015b), Chowdhury et al. (2020) |
| SirReal2 | — | SIRT2 IC50 = 0.14–0.44 μM SIRT1 22% inhibition > 100 μM | SIRT2 inhibitor | Lancelot et al. (2013) |
| Cilostazol | AD | — | SIRT1 activator | Lee et al. (2014), Lee et al. (2019) |
| Salermide | — | SIRT1 IC50 = 43 μM SIRT2 IC50 = 25 μM | Inhibitor- SIRT1 and 2 | Grozinger et al. (2001), Carafa et al. (2016) |
| ICL-SIRT078 | PD | SIRT2 IC50 = 1.45 μM | SIRT2 inhibitor | Di Fruscia et al. (2015) |
| 33i | AD | SIRT1 IC50 > 300 μM SIRT2 IC50 = 0.57 μM | SIRT2 inhibitor | Suzuki et al. (2012), Diaz-Perdigon et al. (2020) |
| 24a | — | SIRT1 IC50 > 100 SIRT2 IC50 = 0.815 μM | SIRT2 inhibitor | Yang et al. (2018) |
| 53 | — | SIRT1 IC50 = 77.4 μM SIRT2 IC50 = 0.31 μM | SIRT2 inhibitor | Mellini et al. (2019) |
| 6 | — | SIRT2 IC50 = 1.74 μM SIRT1 14% inhibition = 50 μM | SIRT2 inhibitor | Li et al. (2014), Mellini et al. (2017) |
| 36 (KPM-2) | — | SIRT1 IC50 = 1.56 μM SIRT2 IC50 = 0.055 μM | SIRT2 inhibitor | Mellini et al. (2019) |
| S1th 13 | — | SIRT1 IC50 = 5.2 μM SIRT2 IC50 = no inhibition > 50 μM | SIRT1 inhibitor | Wössner et al. (2020) |
| γ-mangostin | AD | SIRT1 IC50 = 3.8 μM SIRT2 IC50 = 22.4 μM | SIRT2 inhibitor | Yeong et al. (2020) |
Note: The in vitro IC50 reported for some of the inhibitors above was measured using assays that employ fluorophore-containing substrates that do not always reproduce deacetylation of the native substrate.