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Related Concept Videos

Phase II Reactions: Acetylation Reactions01:24

Phase II Reactions: Acetylation Reactions

Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

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

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...
Phase II Reactions: Sulfation and Conjugation with α-Amino Acids01:19

Phase II Reactions: Sulfation and Conjugation with α-Amino Acids

Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme activation, sulfur...
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation01:22

Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation

Glutathione, a tripeptide made up of glutamate, cysteine, and glycine, is a critical player in the detoxification of drugs and xenobiotics via a process known as glutathione conjugation or mercapturic acid formation. This phase II biotransformation reaction involves the covalent binding of glutathione to a drug or its metabolite, enhancing the compound's water solubility and enabling its excretion.
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems01:19

Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems

Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...

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Related Experiment Video

Updated: Jul 2, 2026

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
09:44

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen

Published on: November 27, 2019

Reprogramming Acetaminophen Metabolism via Amide-to-Thioamide Modification to Prevent Drug-Induced Liver Injury.

Shuanglong Chen1, Jiaxin Chang1, Yubin Sha1

  • 1State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.

Journal of Medicinal Chemistry
|July 1, 2026
PubMed
Summary
This summary is machine-generated.

Researchers developed a modified acetaminophen (APAP) drug, SAPAP, that reduces liver injury by altering its metabolism. This new compound retains pain relief and fever reduction properties while offering a safer alternative to traditional APAP, especially in overdose situations.

Related Experiment Videos

Last Updated: Jul 2, 2026

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
09:44

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen

Published on: November 27, 2019

Area of Science:

  • Medicinal Chemistry
  • Hepatology
  • Pharmacology

Background:

  • Acetaminophen (APAP) overdose is a primary cause of acute liver failure.
  • APAP-induced liver injury stems from its bioactivation to a toxic intermediate (NAPQI) via cytochrome P450 enzymes.
  • Current antidote therapy (N-acetylcysteine) is effective but highly time-sensitive.

Purpose of the Study:

  • To develop a novel APAP analogue that mitigates hepatotoxicity while preserving therapeutic efficacy.
  • To investigate a metabolic reprogramming strategy using amide-to-thioamide modification to reduce APAP bioactivation.
  • To evaluate the safety and efficacy of the synthesized thioamide analogue, SAPAP.

Main Methods:

  • Synthesis of a thioamide-modified APAP analogue (SAPAP).
  • Evaluation of SAPAP's metabolic profile, focusing on bioactivation pathways and conjugation.
  • Assessment of SAPAP's hepatic safety and pharmacological activity in acute overdose and subchronic rodent models.

Main Results:

  • SAPAP demonstrated a metabolic shift away from toxic NAPQI formation, favoring glucuronide and sulfate conjugation.
  • SAPAP significantly reduced liver injury compared to APAP in overdose and subchronic models, evidenced by improved histopathology and lower transaminase levels.
  • SAPAP maintained comparable analgesic and antipyretic efficacy to APAP in established preclinical models.

Conclusions:

  • Thiocarbonyl modification can effectively decouple APAP's therapeutic benefits from its hepatotoxic liabilities.
  • SAPAP represents a promising preventive strategy against acetaminophen-induced liver injury.
  • Metabolic reprogramming offers a viable approach for designing safer drug analogues with reduced toxicity.