Uses
SRT 1720 is a selective activator of human SIRT1 with an EC1.5 of 0.16 μM, and shows less potent activities for SIRT2 and SIRT3 with EC1.5s of 37 μM and > 300 μM, respectively.
General Description
A cell-permeable quinolinecarboxamide compound that is shown to inhibit the mitochondrial SIRT3 in a substrate AceCS2-competitive (
Ki = 0.56 μM;
Km = 2.44 μM), but NAD
+-uncompetitive (
Ki = 0.34 μM;
Km = 280 μM), manner. Also reported to decrease cellular p53 Lys382 acetylation (Effective conc. = 10 μM in U2OS and MEF cultures) and inhibit p300 HAT activity (IC
50 = 9 μM)
in vitro, as well as offer therapeutic benefits in several murine and rodent type 2 diabetes models (100 mg/kg/dayl p.o.)
in vivo. Whether and how SRT1720 activates SIRT1 activity remains uncertain. Also available as a 25 mM solution in DMSO (Cat. No.
530748).
in vivo
SRT 1720 (10, 30, 100 mg/kg, p.o.) significantly reduces the hyperinsulinaemia after 4 weeks, partially normalizing elevated insulin levels similar to rosiglitazone treatment. SRT 1720 treatment significantly reduces fasting blood glucose to near normal levels in Lepob/ob mice[1]. SRT 1720 has ability to protect against the negative effects of diet-induced obesity in mice, and has a connection to metabolic adaptation in fatty acid and oxidative metabolism through downstream targets of SIRT1 such as PGC1α and FOXO1[2]. SRT 1720 (50-100 mg/kg, p.o.), during emphysema development attenuates elastase-induced airspace enlargement and lung function impairment as well as reduces arterial oxygen saturation in WT mice[3].
IC 50
SIRT1: 0.16 μM (EC1.5); SIRT2: 37 μM (EC1.5)
References
[1] Milne JC et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007 Nov 29;450(7170):712-6 DOI:
10.1038/nature06261[2] Baur JA, et al. Are sirtuins viable targets for improving healthspan and lifespan Nat Rev Drug Discov. 2012 Jun 1;11(6):443-61 DOI:
10.1038/nrd3738[3] Yao H, et al. SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice. J Clin Invest. 2012 Jun 1;122(6):2032-45. DOI:
10.1172/JCI60132[4] Yu L, et al. Protective effects of SRT1720 via the HNF1α/FXR signalling pathway and anti-inflammatory mechanisms in mice with estrogen-induced cholestatic liver injury. Toxicol Lett. 2016 Dec 15;264:1-11. DOI:
10.1016/j.toxlet.2016.10.016
![N-[2-[3-(1-Piperazinylmethyl)imidazo[2,1-b]thiazol-6-yl]phenyl]-2-quinoxalinecarboxamide Structure](https://www.chemicalbook.com/CAS/GIF/925434-55-5.gif)
