Related Experiment Video
Updated: May 27, 2026
11:02
Identification and Quantification of Deranged Metabolites in Critically Ill Patients Using NMR-Based Metabolomics
Published on: November 29, 2024
Metabolomics in drug target discovery.
J D Rabinowitz1, J G Purdy, L Vastag
1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA. joshr@genomics.princeton.edu
Cold Spring Harbor Symposia on Quantitative Biology
|November 25, 2011
Summary
Metabolomics and isotope tracers identify new drug targets by revealing disease-related metabolic changes. This approach successfully pinpointed acetyl-CoA carboxylase as a target for human cytomegalovirus, blocking its replication.
Area of Science:
- Biochemistry
- Virology
- Pharmacology
Background:
- Metabolic alterations are common in diseases and can drive progression.
- Metabolomics offers a way to identify pathological metabolic changes for therapeutic intervention.
- Enzymes with increased metabolic flux during disease are promising drug targets.
Purpose of the Study:
- To present techniques for discovering new drug targets using metabolomics and isotope tracers.
- To exemplify these methods in viral pathogen studies.
- To identify novel therapeutic targets for viral infections and cancer.
Main Methods:
- Utilized metabolomic analysis to compare infected versus mock-infected cells.
- Employed isotope tracers to definitively assess metabolic flux.
- Investigated viral pathogens including influenza A, herpes simplex virus, and human cytomegalovirus (HCMV).
Main Results:
- Metabolomics revealed significant metabolic changes around known antiviral targets for influenza A and herpes simplex virus.
- For HCMV, metabolomics identified the tricarboxylic acid (TCA) cycle and fatty acid biosynthesis as key affected areas.
- Isotope tracing showed increased flux through acetyl-CoA carboxylase in HCMV-infected cells; inhibition blocked viral replication.
Conclusions:
- Metabolomics combined with isotope tracers is a powerful strategy for identifying novel drug targets.
- Acetyl-CoA carboxylase is a validated therapeutic target for human cytomegalovirus.
- This approach holds promise for discovering drug targets in various diseases, including cancer.
Related Concept Videos
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
01:26Drug Discovery: Overview
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
01:27Pharmacogenetics of Drug Metabolism: Overview
Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
01:28Drug Biotransformation: Overview
Biotransformation, also known as drug metabolism, is a vital physiological process that chemically alters drugs, facilitating their elimination from the body and terminating their action. This process involves two main phases: phase I and phase II reactions. Phase I reactions, including oxidation, reduction, and hydrolysis, introduce or unmask polar functional groups on the drug molecule, thereby increasing its water solubility. By enhancing water solubility, the drug becomes more hydrophilic...
01:16Drug Biotransformation: Overview
Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
01:29Pharmacogenetics and Pharmacogenomics: Overview
Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...