WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 556064
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.
MedKoo Cat#: 556064
Chemical Formula: C24H28N4O4
Exact Mass: 436.2111
Molecular Weight: 436.512
Elemental Analysis: C, 66.04; H, 6.47; N, 12.84; O, 14.66
Synonym: IXA4; IXA-4; IXA 4;
IUPAC/Chemical Name: N-(1-(2-(methyl(2-(p-tolyloxy)ethyl)amino)-2-oxoethyl)-1H-pyrazol-4-yl)-3-phenoxypropanamide
InChi Key: ZVSKMVAWWBSNOY-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: CC1=CC=C(OCCN(C(CN2N=CC(NC(=O)CCOC3=CC=CC=C3)=C2)=O)C)C=C1
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: 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.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: To be determined
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|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.|
|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/|
|In vivo activity:||TBD|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 436.512 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|Formulation protocol:||1. Grandjean JMD, Madhavan A, Cech L, Seguinot BO, Paxman RJ, Smith E, Scampavia L, Powers ET, Cooley CB, Plate L, Spicer TP, Kelly JW, Wiseman RL. Pharmacologic IRE1/XBP1s activation confers targeted ER proteostasis reprogramming. Nat Chem Biol. 2020 Oct;16(10):1052-1061. doi: 10.1038/s41589-020-0584-z. Epub 2020 Jul 20. PMID: 32690944; PMCID: PMC7502540.|
|In vitro protocol:||1. Grandjean JMD, Madhavan A, Cech L, Seguinot BO, Paxman RJ, Smith E, Scampavia L, Powers ET, Cooley CB, Plate L, Spicer TP, Kelly JW, Wiseman RL. Pharmacologic IRE1/XBP1s activation confers targeted ER proteostasis reprogramming. Nat Chem Biol. 2020 Oct;16(10):1052-1061. doi: 10.1038/s41589-020-0584-z. Epub 2020 Jul 20. PMID: 32690944; PMCID: PMC7502540.|
|In vivo protocol:||TBD|
1: Madhavan A, Kok BP, Rius B, Grandjean JMD, Alabi A, Albert V, Sukiasyan A, Powers ET, Galmozzi A, Saez E, Wiseman RL. Pharmacologic IRE1/XBP1s activation promotes systemic adaptive remodeling in obesity. Nat Commun. 2022 Feb 1;13(1):608. doi: 10.1038/s41467-022-28271-2. PMID: 35105890; PMCID: PMC8807832.
2: Grandjean JMD, Wiseman RL. Small molecule strategies to harness the unfolded protein response: where do we go from here? J Biol Chem. 2020 Nov 13;295(46):15692-15711. doi: 10.1074/jbc.REV120.010218. Epub 2020 Sep 4. PMID: 32887796; PMCID: PMC7667976.