Biochemical and Biophysical Research Communications
Deuterium isotope effects on toluene metabolism. Product release as a rate-limiting step in cytochrome P-450 catalysis
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Cytochrome P450 Enzymes
2018, Comprehensive Toxicology: Third EditionA Decade of Deuteration in Medicinal Chemistry
2017, Annual Reports in Medicinal ChemistryCitation Excerpt :Additionally, as the system increases in complexity (Supersomes™ to microsomes to hepatocytes, etc.), other non-CYP clearance mechanisms may predominate and blunt the observed DIE. Furthermore, reducing CYP metabolism with deuterium at a known site of metabolism can “switch” metabolism to another site, resulting in no observed DIE (no change in clearance) or even an inverse DIE (faster clearance).14–16 For example, maraviroc (3, Fig. 2) is a negative allosteric modulator of the chemokine receptor CCR5 marketed as Selzentry® for the treatment of human immunodeficiency virus infections.
Deuterium in Drug Discovery and Development
2011, Annual Reports in Medicinal ChemistryCitation Excerpt :In practice, the observed DIE, (kH/kD)obs for a metabolic reaction is often “masked”, which means that it is smaller than kH/kD or, in some cases, entirely absent [14]. There are also literature examples of inverse DIEs in which (kH/kD)obs < 1 [15]. A very large number of studies have appeared in the literature over the years reporting DIEs for a great many enzyme-catalyzed reactions.
Cytochrome P450 Enzymes
2010, Comprehensive Toxicology, Second EditionKinetics of cytochrome P450 2E1-catalyzed oxidation of ethanol to acetic acid via acetaldehyde
1999, Journal of Biological ChemistryDiscovery and In Vitro Characterization of SPL028: Deuterated N,N-Dimethyltryptamine
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