Sirtuin (Sir2 proteins) is a class of proteins. And it possesses either mono-ADP-ribosyltransferase, or deacylase activity, including deacetylase, desuccinylase, demalonylase, demyristoylase and depalmitoylase activity. Sirtuins regulate important biological pathways in bacteria, archaea and eukaryotes. Importantly, Sirtuins play an important role in a wide range of cellular processes like aging, transcription, apoptosis, inflammation and stress resistance, as well as energy efficiency and alertness during low-calorie situations. Sirtuins can also control circadian clocks and mitochondrial biogenesis.

SIRT1, also known as NAD-dependent deacetylase sirtuin-1, is an enzyme located primarily in the cell nucleus. Inducing the expression of SIRT1 can increase insulin sensitivity, suggesting the molecule is associated with improving insulin sensitivity. Furthermore, SIRT1 can de-acetylate and affect the activity of both members of the PGC1-alpha/ERR-alpha complex, which are essential metabolic regulatory transcription factors. In mammals, SIRT1 can deacetylate and thereby deactivate the p53 protein. SIRT1 also stimulates autophagy by preventing acetylation of proteins (via deacetylation) required for autophagy as demonstrated in cultured cells and embryonic and neonatal tissues. This function provides a link between sirtuin expression and the cellular response to limited nutrients due to caloric restriction. SIRT1 plays a role in activating T helper 17 cells, which contribute to autoimmune disease; efforts to activate SIRT1 therapeutically may trigger or exacerbate autoimmune disease.

SRTCX1003 is an orally active SIRT1 activator that can inhibit inflammatory responses.

NF-κB plays a significant role in regulating inflammatory cytokine production. Therefore, SRTCX1003 could block LPS-induced TNFα secretion from RAW 264.7 murine macrophage cells. Further, the reduction of TNFα secretion from RAW cells mediated by SRTCX1003 treatment was largely reversed upon knockdown of SIRT1 by siRNA. Thus, STAC-mediated inhibition of LPS-induced inflammatory response is dependent on SIRT1. Furthermore, SRTCX1003 mediates decreases in the production of several proinflammatory cytokines, including TNFα and IL-12, in vivo following the administration of LPS.

All in all, SRTCX1003 is an orally active SIRT1 activator that can suppress inflammatory responses in vivo.


[1] Rahman S, et, al. Cell Commun Signal. 2011 May 8;9:11.

[2] Yang H, et, al. PLoS One. 2012;7(9):e46364.