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Department of Chemistry
St. John's University
8000 Utopia Parkway
Jamaica, NY 11439
Phone 516-883-7510
Fax 516-883-4003
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LONG ISLAND CHEMICAL SOCIETY
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In memoriam
It is with deepest sadness that we mark the passing of our friend and colleague, Prof. Eugene Brown, a former Chair of the Long Island Subsection. |
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Hofstra University
Student Center Plaza West, Room 0127W
(Please note that this is a different room than past seminars at Hofstra)
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Social: 5:45 pm Seminar: 6:15 PM
Dinner: 7:30PM at a nearby restaurant ($25)
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Fall 2010 Events
September 16, 2010 Dr. Melissa Van Alstine, Adelphi UniversityDesign of Fluorometric High-Throughput Screening Assays for Cytochrome P450s The cytochrome P450s (CYPs) are a superfamily of heme-containing enzymes that mediate the metabolism of endogenous and exogenous molecules. Most studies on CYPs have been driven by drug-drug interactions and involve human isoforms. Recently, fluorometric high-throughput screens (HTS) have been developed for major human drug-metabolizing CYPs (CYP1-4) and used to screen drugs for CYP inhibition, but applications of these methods for rat P450s have been limited. We have developed a fluorometric HTS specifically for the cDNA-expressed rat CYP2B1, CYP2C6 and CYP2C11 using the substrate 7-ethoxy-4-trifluoromethylcoumarin (EFC) or dibenzylfluorescein (DBF). A series of inhibitors were then characterized on these rat P450s as well as some human P450s (CYP2C19 and CYP2B6). IC50 values were determined for some imidazole-containing analgesic antagonists (CC12 and MW-06-25), antifungal drugs (miconazole, sulconazole, clotrimazole, ketoconazole and fluconazole) and epoxygenase inhibitors (MSPPOH and PPOH). MS-PPOH and PPOH displayed time- and NADPH-dependent inactivation, suggesting that these compounds are mechanism-based inhibitors. |
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