MOL #109744 The X-ray Crystal Structure of the Human Monooxygenase Cytochrome P450 3A5-Ritonavir Complex Reveals Active Site Differences between P450s 3A4 and 3A5
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The X-Ray Crystal Structure of the Human Mono-Oxygenase Cytochrome P450 3A5-Ritonavir Complex Reveals Active Site Differences between P450s 3A4 and 3A5.
The contributions of cytochrome P450 3A5 to the metabolic clearance of marketed drugs is unclear, but its probable role is to augment the metabolism of several drugs that are largely cleared by P450 3A4. Selective metabolism by 3A4 is often a concern in drug development owing to potential drug-drug interactions and the variability of 3A4 and 3A5 expression. The contribution of P450 3A5 to these...
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Sirolimus is an immunosuppressive drug currently used alone or in combination with cyclosporine. Both drugs undergo extensive metabolism by the CYP 3A enzymes. This study aimed at comparing the activity of recombinant CYP (rCYP) 3A4 and 3A5 toward sirolimus, investigating the effect of cyclosporine on the metabolic rate of these two cytochromes P450 (P450s), as well as the impact of the CYP 3A5...
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The metabolic activation of estrone (E1), a potent estrogen was investigated using recombinant human cytochrome P450 enzymes, 1A2, 2B6, 2C8, 2C9, 2C9R144C, 2E1, 3A4, 3A5 and liver microsomes from 14 human organ donors. At least five products of E1 were detected and quantitated by HPLC and gas chromatography-mass spectrometry (GC-MS). Among these metabolites, 16alpha-OH-E1, 2-OH-E1 and 4-OH-E1, ...
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An investigational anticancer agent that contains a thiophene moiety, 3-[(quinolin-4-ylmethyl)-amino]-N-[4-trifluoromethox)phenyl] thiophene-2-carboxamide (OSI-930), was tested to investigate its ability to modulate the activities of several cytochrome P450 enzymes. Results showed that OSI-930 inactivated purified, recombinant cytochrome P450 (P450) 3A4 in the reconstituted system in a mechanis...
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The principal enzyme involved in the oxidation of mifepristone is cytochrome P450 3A4 (CYP3A4), which undergoes mechanism-based inactivation by the drug. However, no information is available on the interaction with CYP3A5, the second most abundant CYP3A enzyme in adult human liver. Oxidation of mifepristone by recombinant CYP3A4 produced mono- and didemethylated products and one C-hydroxylated ...
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تاریخ انتشار 2017