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.
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 分子式: C22H17F4NO2
- 分子量:403.37
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
生物活性
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LXRβ 45 nM (EC50) |
PPARδ 40 nM (EC50) |
PPARα 10 mM (EC50) |
PPARγ 305 nM (EC50) |
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.
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.
化学情報
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分子量 403.37
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分子式 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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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)