IXA4 |
Katalog-Nr.GC63785
One-Click Copy Product Info
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IXA4 ist ein hochselektiver, ungiftiger IRE1/XBP1s-Aktivator.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1185329-96-7
Sample solution is provided at 25 µL, 10mM.
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IXA4 is a highly selective, non-toxic IRE1/XBP1s activator that induces endoplasmic reticulum (ER) proteostasis remodeling[1]. IXA4 activates IRE1/XBP1 signaling but does not fully activate the unfolded protein response (UPR) or other stress response signaling pathways[2]. IXA4 reduces the secretion of amyloid precursor protein (APP) through IRE1 activation and prevents APP-related mitochondrial dysfunction[3].
In vitro, IXA4 (30μM) treatment of mouse splenic T cells for 4 days significantly increased mitochondrial mass and mitochondrial ATP reserves in cells[4]. IXA4 (10μM) treatment of CHO7PA2 cells expressing the V717F APP (APPV717F) mutant for 18h reduced the level of β-amyloid protein (Aβ) by 50%[5].
In vivo, IXA4 (50mg/kg) was treated with diet-induced obese (DIO) mice by intraperitoneal injection for 8 weeks, which selectively activated IRE1/XBP1s signaling in the liver of mice, improved glucose homeostasis, inhibited hepatic gluconeogenesis, and reduced the expression of key lipogenic genes in the liver (including Dgat2, Scd1, and Srebf1c)[6].
References:
[1] Siwecka N, Rozpędek-Kamińska W, Wawrzynkiewicz A, et al. The structure, activation and signaling of IRE1 and its role in determining cell fate[J]. Biomedicines, 2021, 9(2): 156.
[2] Wang H, Karnati S, Madhusudhan T. Regulation of the homeostatic unfolded protein response in diabetic nephropathy[J]. Pharmaceuticals, 2022, 15(4): 401.
[3] Cummins N, Taylor R C. A stress-free stress response[J]. Nature Chemical Biology, 2020, 16(10): 1038-1039.
[4] Riesenberg B P, Gandy E J, Kennedy A S, et al. Adaptive IRE1 Signaling Elicits T Cell Metabolic Remodeling and Tumor Control[J]. bioRxiv, 2023: 2023.11. 16.567431.
[5] Grandjean J M D, Madhavan A, Cech L, et al. Pharmacologic IRE1/XBP1s activation confers targeted ER proteostasis reprogramming[J]. Nature chemical biology, 2020, 16(10): 1052-1061.
[6] Madhavan A, Kok B P, Rius B, et al. Pharmacologic IRE1/XBP1s activation promotes systemic adaptive remodeling in obesity[J]. Nature communications, 2022, 13(1): 608.
| Cell experiment [1]: | |
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Cell lines |
T cells |
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Preparation Method |
Whole splenocytes from OT-1 mice were activated with 1μg/mL OVA peptide and expanded for 3 days with 200U/mL rhIL-2 (NCI) then split and expanded for 4 more days. IXA4 (30μM) was added at T cell activation and again at the cell split for 4 more days. Cell mitochondria were labeled with MitoTracker and then analyzed by confocal imaging and flow cytometry. |
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Reaction Conditions |
30μM; 4 days |
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Applications |
IXA4 treatment increased mitochondrial mass and mitochondrial ATP reserves in T cells. |
| Animal experiment [2]: | |
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Animal models |
Diet-induced obese (DIO) mice |
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Preparation Method |
Diet-induced obese (DIO) mice were maintained on a high-fat diet for 3 weeks. IXA4 was formulated in 10% DMSO, 30% Kolliphor EL:ethanol (2:1 ratio), 60% saline. Mice were given vehicle, IXA4 (50mg/kg) once daily by intraperitoneal injection for up to 8 weeks. Body weight and food intake were measured weekly. At sacrifice, tissues were harvested and snap frozen for processing. |
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Dosage form |
50mg/kg/day, for 8 weeks; i.p. |
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Applications |
IXA4 selectively activated IRE1/XBP1s signaling in the liver of DIO mice, improved glucose homeostasis, inhibited hepatic gluconeogenesis, and reduced the expression of key lipogenic genes in the liver, including Dgat2, Scd1, and Srebf1c. |
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References: |
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| Cas No. | 1185329-96-7 | SDF | |
| Formula | C24H28N4O4 | M.Wt | 436.5 |
| Löslichkeit | DMSO : 100 mg/mL (229.10 mM; Need ultrasonic) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.291 mL | 11.4548 mL | 22.9095 mL |
| 5 mM | 458.2 μL | 2.291 mL | 4.5819 mL |
| 10 mM | 229.1 μL | 1.1455 mL | 2.291 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 32 reference(s) in Google Scholar.)