AU403
AU403 is a potent, brain-penetrant, isoform-selective LXRβ/PPARδ dual agonist (EC50 ≈ 45 nM for LXRβ and EC50 ≈ 40 nM for PPARδ). AU403 is designed to bypass LXRα-driven hepatotoxicity. AU403 significantly improves cognitive functions and reduces amyloid-β plaque burden in 3xTg-AD mice. AU403 is a promising dual-acting agonist for the research of Alzheimer’s disease.
For research use only. We do not sell to patients.
- Formula: C22H17F4NO2
- Molecular Weight:403.37
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
LXRβ 45 nM (EC50) |
PPARδ 40 nM (EC50) |
PPARα 10 mM (EC50) |
PPARγ 305 nM (EC50) |
In Vitro
AU403 (1-20 μM; 24 h) exhibits potent, dose-dependent activation of LXRβ, with an EC50 of 45 nM, while demonstrating significantly reduced potency toward LXRα (EC50 = 400 nM) in HEK293 cells[1].
AU403 (1-20 μM; 24 h) exhibits partial agonistic activity at PPARδ (EC50 ∼ 40 nM), exhibits weak activity toward PPARα (EC50 ∼ 10 μM) and shows moderate agonistic activity toward PPARγ (EC50 of ∼ 350 nM) in HEK293 cells[1].
AU403 (1-20 μM; 24 h) robustly induces promoter activity and drive key cholesterol transporters in HEK293 cells[1].
AU403 (5-20 μM; 24 h) modulates pathways central to hepatocyte biology, including cytochrome P450 (CYP) enzymes, lipid metabolism, and cholesterol homeostasis, without promoting the transcription of key lipogenic drivers (FASN and SREBF1) in human primary hepatocytes, thereby successfully mitigating the lipogenic risks associated with LXR activation [1].
AU403 (0.01-100 μM) has no significant effect on neutropenia or total erythroid levelsat its LD50 of 55 μM, while preserving hematopoietic progenitor cell activity without impacting erythropoiesis in bone marrow-derived erythroid progenitor cells[1].
AU403 exhibits no cardiotoxic effect in the hERG assay, with an IC50 of 22 μM[1].
AU403 (1-10 μM) significantly reduces Aβ secretion, and this mechanism may work in concert with the upregulation of ABC transporters to promote the clearance of Aβ plaques in APP-CHO cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
AU403 (10 mg/kg; i.p.; once a day; 30 days) successfully mitigates the lipogenic risks associated with LXR activation in C57BL/6 mice[1].
AU403 (10 mg/kg; i.p.; once a day; 3 months) improves recognition memory in behavioral assays (NOR and Y-Maze), restores hippocampal synaptic plasticity, and reduces Aβ1-42 levels in 3xTg-AD mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Three-month-old C57BL/6 mice[1].
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Dosage:10 mg/kg
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Administration:i.p.; once a day; 30 days
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Result:Resulted in no significant elevations in circulating triglycerides or total cholesterol.
Showed serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) remained within baseline ranges.
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Animal Model:Nine-month-old 3xTg-AD mice B6;129-Tg[1].
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Dosage:10 mg/kg
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Administration:i.p.; once a day; 3 months
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Result:Exhibited no biased object preference and indicated comparable baseline exploration behavior in the NOR training session.
Significantly increased novel object exploration.
Significantly restored the discrimination index reduction and improved short-term declarative memory.
Demonstrated a trend toward behavioral improvement, suggesting partial restoration of spatial recognition.
Enhanced both the field excitatory postsynaptic potential (fEPSP) slopes and LTP magnitude (p < 0.0048) significantly.
Showed no reduced fEPSP amplitude during θ-burst stimulation.
Showed a reduction in levels of Aβ.
Reduced (~45%) the soluble form of Aβ1-42 significantly.
Chemical Information
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Molecular Weight 403.37
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Formula C22H17F4NO2
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SMILES
OC(C1=CC(CNCC2=C(C3=CC(C(F)(F)F)=CC=C3)C=CC=C2F)=CC=C1)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Hepatotoxicity Study
This protocol evaluates hepatotoxicity using complementary in vivo mouse APAP acute liver injury and in vitro hepatocyte-based cytotoxicity readouts. In vivo APAP injury is assessed by serum ALT/AST, liver histology, hepatic glutathione, protein adducts, necrosis, inflammation, and regeneration-related endpoints. In vitro hepatotoxicity is assessed by loss of viability, leakage of ALT/AST/LDH, oxidative-stress markers, mitochondrial function, nuclear morphology, intracellular calcium, and high-content imaging endpoints.
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Amyloid: Congo Red Amyloid Staining
Congo red amyloid staining is a histochemical method used to detect extracellular amyloid deposits in tissue sections based on the affinity of Congo red dye for β-pleated sheet-rich protein aggregates. When bound to amyloid, Congo red produces characteristic apple-green birefringence under polarized light microscopy, which is widely regarded as a diagnostic feature of amyloid deposition in histopathology. The diagnostic principle relies on the combination of dye binding (congophilia) and optical anisotropy under polarized illumination, which distinguishes amyloid from most non-amyloid eosinophilic extracellular deposits in routine histological evaluation. Amyloid identification by Congo red staining remains a cornerstone in diagnostic pathology despite the availability of adjunct methods such as immunohistochemistry and mass spectrometry, particularly because of its ability to localize deposits directly within tissue architecture. The specificity of Congo red-positive deposits is incre
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Alzheimer’s Disease Modeling
Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive functions and loss of specific types of neurons and synapses. Alzheimer's symptoms can be simulated in mice by injecting drugs (such as Aβ) or genetically modified.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)