Oxetane Substrates of Human Microsomal Epoxide Hydrolase
نویسندگان
چکیده
منابع مشابه
Oxetane Substrates of Human Microsomal Epoxide Hydrolase.
Oxetanyl building blocks are increasingly used in drug discovery because of the improved drug-like properties they confer on drug candidates, yet little is currently known about their biotransformation. A series of oxetane-containing analogs was studied and we provide the first direct evidence of oxetane hydrolysis by human recombinant microsomal epoxide hydrolase (mEH). Incubations with human ...
متن کاملMicrosomal epoxide hydrolase polymorphisms.
Microsomal epoxide hydrolase plays a dual role in the activation and detoxification of carcinogenic compounds. Two polymorphic sites have been described in exons 3 and 4 of the microsomal epoxide hydrolase gene that change tyrosine residue 113 to histidine (Tyr113His) and histidine 139 to arginine (His139Arg), respectively. The exon 3 polymorphism reduces enzyme activity by approximately 50%, w...
متن کاملDiscovery of a Novel Microsomal Epoxide Hydrolase-Catalyzed Hydration of a Spiro Oxetane.
Oxetane moieties are increasingly being used by the pharmaceutical industry as building blocks in drug candidates because of their pronounced ability to improve physicochemical parameters and metabolic stability of drug candidates. The enzymes that catalyze the biotransformation of the oxetane moiety are, however, not well studied. The in vitro metabolism of a spiro oxetane-containing compound ...
متن کاملVisualization of a covalent intermediate between microsomal epoxide hydrolase, but not cholesterol epoxide hydrolase, and their substrates.
Mammalian soluble and microsomal epoxide hydrolases have been proposed to belong to the family of alpha/beta-hydrolase-fold enzymes. These enzymes hydrolyse their substrates by a catalytic triad, with the first step of the enzymatic reaction being the formation of a covalent enzyme-substrate ester. In the present paper, we describe the direct visualization of the ester formation between rat mic...
متن کاملFunctional analysis of human microsomal epoxide hydrolase genetic variants.
Human microsomal epoxide hydrolase (EPHX1) is active in the metabolism of many potentially carcinogenic or otherwise genotoxic epoxides, such as those derived from the oxidation of polyaromatic hydrocarbons. EPHX1 is polymorphic and encodes allelic variation at least two amino acid positions, Y113H and H139R. In a number of recent molecular epidemiological investigations, EPHX1 polymorphism has...
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ژورنال
عنوان ژورنال: Drug Metabolism and Disposition
سال: 2017
ISSN: 0090-9556,1521-009X
DOI: 10.1124/dmd.117.076489