GAA-4OH
GAA-4OH is a potent and irreversible dihydroceramide desaturase-1 (DES1) inhibitor with an IC50 of 0.6 μM and a Ki of 139.5 nM. GAA-4OH undergoes oxidation to form a reactive iminoquinone that covalently blocks DES1’s catalytic cavity, causing permanent enzyme inactivation. GAA-4OH modulates sphingolipid balance by reducing ceramide-to-dihydroceramide ratios in liver tissue. GAA-4OH improves liver steatosis, inflammation, fibrosis, and reduces pro-inflammatory and pro-fibrogenic gene expression. GAA-4OH can be used for the research of metabolic dysfunction-associated steatotic liver disease (MASLD).
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
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: C33H43NO4
- 分子量:517.70
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
GAA-4OH (0.1-50 μM; 2 h) directly and nonallosterically inhibits DES1 activity in mouse liver microsomes with an IC50 of 0.6 μM and a Ki of 139.5 nM[1].
GAA-4OH (5 μM; 2 h) irreversibly inhibits DES1 activity in Huh7 cell extracts, with no activity recovery up to 24 h post-treatment[1].
GAA-4OH (1-20 μM; 2-8 h) inhibits DES1 activity in Huh7 cell cultures, reducing the Cer/dhCer ratio by 91% at 5 μM over 8 h, with activity detectable as early as 2 h post-treatment[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
GAA-4OH (150-450 mg/kg; i.p.; daily; 8 days) shows no hepatotoxicity in healthy mice, with only mild body weight reduction at the highest tested dose[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Metabolic dysfunction-associated steatotic liver disease (MASLD) C57BL/6J mice (male, 6 weeks old, fed high-fat diet plus high sugar drinking water for 16, 22, or 30 weeks)[1]
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Dosage:30 mg/kg
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Administration:i.p.; thrice weekly; 8 weeks
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Result:Reduced liver ratios of Cer/dhCer, SM/dhSM, and HexCer/dhHexCer in all high-fat diet groups.
Increased dhCer, dhSM, and dhHexCer concentrations.
Caused no significant effect on total Cer, SM, or HexCer class concentrations.
Prevented weight gain and reduced liver mass in the 22-week high-fat diet group.
Reduced steatosis area in the 16-week and 22-week high-fat diet groups, with corresponding reductions in hepatic triglyceride and cholesteryl/steryl ester concentrations.
Reduced plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the 22-week high-fat diet group.
Increased blood platelet counts in the 16-week high-fat diet group.
Lowered steatosis, inflammation, and fibrosis scores across all high-fat diet groups via histological scoring.
Led to resolved or reduced fibrosis in 37% of treated mice per the FLIP algorithm.
Significantly reduced hepatic gene expression of fatty acid synthesis genes (Scd1, Fgf1), inflammatory genes (Tnfa, Mcp1), and fibrogenic genes (Acta2, Tgfb1, Col1a1, Timp1), with the strongest effects in the 16-week high-fat diet group, reduced effects in the 22-week group, and no effects in the 30-week group.
Caused no significant changes in hepatic oxidative stress markers (malondialdehyde, GSSG/GSH ratio).
化学情報
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分子量 517.70
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分子式 C33H43NO4
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SMILES
CC1=CC(O)=CC2=C1O[C@@](C)(CC2)CC/C=C(CC/C=C(CC/C=C(C(NC3=CC=C(C=C3)O)=O)\C)\C)\C
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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)
GAA-4OH 関連分類
HY-183723 関連分類
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