2. Metabolic Enzyme/Protease Neuronal Signaling
  3. Dihydroceramide Desaturase 1 (DES1)
  4. 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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GAA-4OH

GAA-4OH Chemical Structure

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GAA-4OH Related Antibodies

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Description

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)[1].

In Vitro

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 Related Antibodies
In Vivo

GAA-4OH (30 mg/kg; i.p.; thrice weekly; 8 weeks) inhibits hepatic DES1 activity in MASLD mice, reduces liver steatosis, inflammation, and fibrosis, and lowers plasma markers of liver damage, with the greatest efficacy in early-to-mid-stage disease[1].
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.

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]
Dosage: 30 mg/kg
Administration: i.p.; thrice weekly; 8 weeks
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).
Molecular Weight

517.70

Formula

C33H43NO4
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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GAA-4OH Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

GAA-4OHDihydroceramide Desaturase 1 (DES1)Dihydroceramide Desaturase 1DES1DEGS1mouse liver microsomesdihydroceramide desaturase-1Huh7 cell extractsMASLDliver tissueAML12 cellsHuh7 cell culturesmousemetabolic dysfunction-associated steatotic liver diseaseInhibitorinhibitorinhibit

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