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).
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- 화학식: C33H43NO4
- 분자량:517.70
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
Biological Activity
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).
Chemical Information
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분자량 517.70
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화학식 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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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GAA-4OH Related Classifications
HY-183723 Related Classifications
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