What is a reactive metabolite? Reactive metabolites are usually electron deficient molecules and are referred to as electrophiles (molecules containing positive centers). If not detoxified properly, these electrophiles can react with electron rich species, i.e.
What is a reactive metabolite?
Reactive metabolites are usually electron deficient molecules and are referred to as electrophiles (molecules containing positive centers). If not detoxified properly, these electrophiles can react with electron rich species, i.e. nucleophiles (molecules containing negative centers), through covalent bond formation.
Can metabolites be toxic?
However, when some substances are metabolized, the resulting metabolites are toxic to the body and can cause fatal results.
What is GSH trapping?
Our fully validated Glutathione (GSH) Trapping assay is based upon microsomal incubation of parent compound in the presence of an excess of reduced glutathione. Reactive metabolites formed during the incubation are trapped by GSH and are detected using high resolution mass spectrometry.
What is an effect of Bioactivation?
Formation of harmful or highly reactive metabolic from relatively inert/nontoxic chemical compounds is called bioactivation or toxication. The bioactive metabolites often interact with the body tissues to precipitate one or more forms of toxicities such as carcinogenesis, teratogenesis, and tissue necrosis.
What are metabolites?
Listen to pronunciation. (meh-TA-boh-lite) A substance made or used when the body breaks down food, drugs or chemicals, or its own tissue (for example, fat or muscle tissue). This process, called metabolism, makes energy and the materials needed for growth, reproduction, and maintaining health.
What are harmful metabolites?
Metabolite damage can occur through enzyme promiscuity or spontaneous chemical reactions. Many metabolites are chemically reactive and unstable and can react with other cell components or undergo unwanted modifications. Enzymatically or chemically damaged metabolites are always useless and often toxic.
What are the types of metabolites?
The metabolites can be grouped into two major types: primary and secondary. Primary metabolites are those that are directly involved in the growth, development, and reproduction of an organism whereas secondary metabolites are those that are not.
How are metabolites detected?
High-throughput analytical platforms such as nuclear magnetic resonance (NMR) spectroscopy, gas chromatography (GC), and/or liquid chromatography (LC) coupled to mass spectrometry (MS) are employed to measure the metabolites within the biological matrix [6, 7].
Can we predict toxicities of drug candidates that form reactive metabolites?
Dealing with Reactive Metabolites in Drug Discovery: Can we Predict Toxicities of Drug Candidates that form Reactive Metabolites? Deepak Dalvie Pharmacokinetics, Dynamics and Metabolism Department Pfizer Addressing Reactive Metabolites in drug discovery has become regular routine 9/28/2016 9
What causes reactive metabolite formation in the body?
Reactive metabolite formation is thought to be one of the primary causes of idiosyncratic adverse drug reactions, often associated with drug-induced skin, liver and hematopoietic toxicities.
How are chemical trapping agents used to identify reactive metabolites?
Chemical trapping agents, such as reduced glutathione (GSH), can form stable adducts with many reactive species. Trapping agents, incubated with liver microsomes, are now routinely used in the identification of reactive metabolites.
When to screen for reactive metabolite in lead optimization?
To minimize the risk of later stage failure – which is of considerable financial burden to the Pharmaceutical Industry – screening for reactive metabolite formation at an early stage in lead optimization is now common practice 1. Chemical trapping agents, such as reduced glutathione (GSH), can form stable adducts with many reactive species.