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Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

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Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...

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Assays for Validating Histone Acetyltransferase Inhibitors
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Entacapone Ameliorates MASLD by Inhibiting FTO Demethylase Activity.

Sunita Giri1, Deepti Sharma2, Vijay Kumar1

  • 1Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.

Drug Development Research
|June 9, 2026
PubMed
Summary
This summary is machine-generated.

Entacapone, an FTO inhibitor, reduced obesity and liver fat in a metabolic dysfunction-associated steatotic liver (MASLD) mouse model. This suggests entacapone

Keywords:
MASHMASLDentacaponem6A modificationmetabolic gene expression

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Area of Science:

  • Hepatology
  • Molecular Biology
  • Pharmacology

Background:

  • Metabolic dysfunction-associated steatotic liver (MASLD) is a chronic liver disease with no standard treatment.
  • Elevated FTO expression is linked to hepatic steatosis and MASLD development.

Purpose of the Study:

  • To investigate the hepatoprotective effects of entacapone, an FTO inhibitor, in preclinical MASLD models.
  • To assess entacapone's impact on obesity, lipid accumulation, liver fibrosis, and metabolic functions.

Main Methods:

  • Administration of entacapone (10 or 30 mg/kg/day) to a MASLD mouse model.
  • Monitoring of obesity, hepatic lipid accumulation, and fibrosis markers.
  • Analysis of hepatic and metabolic function biomarkers, gene/protein expression (FTO, m6A), and immunohistochemical staining.

Main Results:

  • Entacapone treatment significantly reduced obesity, hepatic fat accumulation, and normalized metabolic functions and MAS scores in mice.
  • High m6A levels correlated with reduced FTO, lipogenic, and inflammatory gene expression.
  • FTO isoforms were overexpressed in MASLD patients; entacapone down-regulated FTO expression in hepatocytes.

Conclusions:

  • Entacapone demonstrates therapeutic potential for MASLD by inhibiting FTO demethylase activity.
  • Targeting FTO with entacapone offers a promising strategy for managing metabolic liver diseases.