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Abstract Some inhibitory agents against CYP2B6 have been reported, but none of these has been extensively characterized or compared with others, as to the potency and selectivity of inhibition toward CYP2B6. The goal of this work was to find a selective and potent chemical in vitro inhibitor...
Abstract The measurement of the effect of new chemical entities on human cytochrome P450 marker activities using in vitro experimentation represents an important experimental approach in drug development. In vitro drug interaction data can be used in guiding the design of clinical drug...
Abstract Cytochrome P450 (P450) monooxygenases play a role in target tissue metabolic activation of xenobiotics and/or endogenous compounds, such as vasoactive molecules or hormones. Indeed, tissue-specific metabolism of steroids is important in a variety of organs, including thymus, and may...
Abstract Silybin, a major constituent of the milk thistle, is used to treat several liver disorders. Silybin inactivated purified, recombinant cytochromes P450 (P450) 3A4 and 2C9 in a mechanism-based manner. The inactivations were time-, concentration-, and NADPH-dependent. The inactivation of...
Abstract 3,3′-Diindolylmethane (DIM) is a naturally occurring indole, which is currently under investigation as a potential chemopreventive agent. The concentrations of DIM in plasma, liver, kidney, lung, heart, and brain tissues were determined following oral administration of two different...
Abstract (-)- N -3-Benzyl-phenobarbital (NBPB) was reported to be a potent and selective inhibitor of CYP2C19. To validate the selectivity of NBPB toward CYP2C19 in human liver microsomes, the inhibitory effects on major cytochrome P450 isoform-specific reactions were evaluated in the present...
Abstract There has been very limited information on the capacities of tropical fruits to inhibit human cytochrome P450 3A (CYP3A) activity. Thus, the inhibitory effects of tropical fruits on midazolam 1′-hydroxylase activity of CYP3A in human liver microsomes were evaluated. Eight tropical...
Abstract We investigated cytochrome P450 (P450)-catalyzed metabolism of the important cancer drugs paclitaxel and docetaxel in rat, pig, minipig, and human liver microsomes and cDNA-expressed P450 enzymes. In rat microsomes, paclitaxel was metabolized mainly to C3′-hydroxypaclitaxel (C3′-OHP)...
Abstract Aromatic hydrocarbon (AH) effects are mediated by binding of the AH receptor and its heterodimeric partner aromatic hydrocarbon nuclear translocator to specific response elements on DNA (AHREs). CYP1A2 expression is induced by AHs, yet AHREs have been identified in CYP1A2 genes of only...
Abstract 2-Amino-3-methyl-9 H -pyrido2,3- b indole (MeAαC) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeAαC can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in...
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