Catalog Number
ACM1185329967
Description
IXA4 is a highly selective, non-toxic IRE1/XBP1s activator. IXA4 transiently activates protective IRE1/XBP1s signaling in liver without inducing RIDD or TRAF2/JNK signaling. IXA4 treatment improves systemic glucose metabolism and liver insulin action through IRE1-dependent remodeling of the hepatic transcriptome that reduces glucose production and steatosis. IXA4-stimulated IRE1 activation also enhances pancreatic function. Our findings indicate that systemic, transient activation of IRE1/XBP1s signaling engenders multi-tissue benefits that integrate to mitigate obesity-driven metabolic dysfunction.
Synonyms
IXA4; IXA-4; IXA 4
IUPAC Name
N-(1-(2-(methyl(2-(p-tolyloxy)ethyl)amino)-2-oxoethyl)-1H-pyrazol-4-yl)-3-phenoxypropanamide
Molecular Formula
C24H28N4O4
Canonical SMILES
CC1=CC=C(OCCN(C(CN2N=CC(NC(=O)CCOC3=CC=CC=C3)=C2)=O)C)C=C1
InChI
InChI=1S/C24H28N4O4/c1-19-8-10-22(11-9-19)32-15-13-27(2)24(30)18-28-17-20(16-25-28)26-23(29)12-14-31-21-6-4-3-5-7-21/h3-11,16-17H,12-15,18H2,1-2H3,(H,26,29)
InChI Key
ZVSKMVAWWBSNOY-UHFFFAOYSA-N
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Storage
Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
Biological Target
IXA4 is a highly selective, non-toxic IRE1/XBP1s activator. IXA4 (10 μM; 4 hours) selectively upregulates XBP1s mRNA, relative to genes regulated by ATF6 (e.g., BiP) or PERK (e.g., CHOP), in other cell lines including Huh7 and SHSY5Y cells.
Drug Formulation
To be determined
Elemental Analysis
C, 66.04; H, 6.47; N, 12.84; O, 14.66
HS Tariff Code
2934.99.9001
In Vitro Activity
IXA4 reduced Aβ levels 50% in conditioned media prepared on CHO7PA2 cells expressing the V717F APP (APPV717F) mutant (Fig. 5B). This study confirmed compound-dependent IRE1/XBP1s activation in these cells by qPCR (Extended Data Fig. 7C).
Reference: Nat Chem Biol. 2020 Oct;16(10):1052-1061. https://pubmed.ncbi.nlm.nih.gov/32690944/
Shipping
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Stock Solution Storage
0-4 °C for short term (days to weeks), or -20 °C for long term (months).
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