N-[2-[3-(1-Piperazinylmethyl)imidazo[2,1-b]thiazol-6-yl]phenyl]-2-quinoxalinecarboxamide

Product NameN-[2-[3-(1-Piperazinylmethyl)imidazo[2,1-b]thiazol-6-yl]phenyl]-2-quinoxalinecarboxamide
CAS925434-55-5
MFC25H23N7OS
MW469.56
EINECS
MOL File925434-55-5.mol

Chemical Properties

Melting point	221℃
Density	1.46
storage temp.	-20C
solubility	DMSO:5.0(Max Conc. mg/mL);10.65(Max Conc. mM)
form	Yellow solid
pka	11.19±0.70(Predicted)
color	Light yellow to yellow
InChIKey	IASPBORHOMBZMY-UHFFFAOYSA-N
SMILES	O=C(C1=NC(C=CC=C2)=C2N=C1)NC3=CC=CC=C3C4=CN5C(SC=C5CN6CCNCC6)=N4

Safety Information

WGK Germany	WGK 3
Storage Class	11 - Combustible Solids

Usage And Synthesis

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 (K_i = 0.56 μM; K_m = 2.44 μM), but NAD⁺-uncompetitive (K_i = 0.34 μM; K_m = 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 (IC₅₀ = 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 Lep^ob/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)

storage

Store at -20°C

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

Preparation Products And Raw materials

N-[2-[3-(1-Piperazinylmethyl)imidazo[2,1-b]thiazol-6-yl]phenyl]-2-quinoxalinecarboxamide Supplier

N-[2-[3-(1-Piperazinylmethyl)imidazo[2,1-b]thiazol-6-yl]phenyl]-2-quinoxalinecarboxamide manufacturers

Related Product Information

Send Inquriy