Selisistat (EX-527) is a potent and selective SirT1 (Sir2 in Drosophila melanogaster) inhibitor with an IC50 of 123 nM for SirT1, which alleviates pathology in multiple animal and cell models of Huntington's disease[1].[2].
体内研究
Administered orally at doses of 5 and 20 mg/kg daily to transgenic R6/2 mice from 4.5 weeks of age until death, Selisistat provides protection in models of Huntington’s disease (HD)[1].
体外研究
In cellular assays, Selisistat, at concentrations ranging from 1-10 μM, blocks the deacetylation functions of SirT1 in humans and Sir2 in Drosophila melanogaster within transfected cells[1].
Selisistat 细胞实验
Cell Line
Concentration
Treated Time
Description
References
mouse astrocytes
10 μM
30 min
To investigate the inhibitory effect of Selisistat on IL-1β-induced astrocyte activation. Results showed that Selisistat significantly inhibited IL-1β-induced astrocyte activation.
Neural Regen Res. 2021 Apr;16(4):721-726.
HepG2 cells
40 µM
8 h
To validate the effect of Selisistat as a SIRT1 inhibitor
Hepatol Commun. 2020 Jan 16;4(3):434-449.
HT22 cells
1 μM
2 h
To evaluate the effect of Selisistat on the Sirt1/FoxO1/Rab7 axis, it was found that Selisistat significantly reduced the expression of Sirt1, Rab7, and FoxO1 and inhibited autophagosome formation.
Cells. 2022 Nov 21;11(22):3701.
human skeletal stem cells (hSSCs)
1 µM
14 days
To investigate the inhibitory effect of Selisistat on osteogenic differentiation of hSSCs, results showed that Selisistat significantly reduced the osteogenic differentiation capacity of hSSCs.
Aging Cell. 2020 Jul;19(7):e13164.
Selisistat 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Early social isolation (ESI) model
Oral gavage
20 mg/kg
Once daily for 12 days
To investigate the effect of Selisistat on depression-like behavior in adult mice when administered during early development. Results showed that Selisistat administration during juvenility increased immobility and decreased activity in the FST in control mice, while no significant changes were observed in ESI mice.
Transl Psychiatry. 2015 Sep 1;5(9):e629
Mice
Nigrostriatal pathway injury model
Intraperitoneal injection
5 mg/kg
Single dose, 30 minutes before injury
To investigate the neuroprotective effect of Selisistat after nigrostriatal pathway injury. Results showed that Selisistat significantly reversed the neuroprotective effects of Batroxobin.
Neural Regen Res. 2021 Apr;16(4):721-726.
Mice
Diabetic and obese model
Oral
10 mg/kg
Once daily for 4 weeks
TMS alleviated endothelial dysfunction in diet-induced obese mice by enhancing the AMPK/SIRT1/eNOS pathway and attenuating oxidative stress and ER stress in aortas.
Antioxidants (Basel). 2022 Jun 28;11(7):1286
Mice
Sepsis model
Intraperitoneal injection
5 mg/kg
Selisistat (EX-527) inhibited the expression of Sirt1 and partially reversed the upregulation of Sirt1 by NMN.
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