A comparative study of the CYP450 inhibition potential of marketed drugs using two fluorescence based assay platforms routinely used in the pharmaceutical industry

Mahmud Kajbaf (Lead / Corresponding author), Raffaele Longhi (Research group member), Dino Montanari (Research group member), Federica Vinco (Research group member), Monica Rigo (Research group member), Stefano Fontano (Research group member), Kevin D. Read

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    Abstract

    Semi-automated high throughput screening for the inhibition of major human cytochrome P450 enzymes (1A2, 2C9, 2C19, 2D6 and 3A4) expressed in Escherichia Coli (Cypex bactosomes) or human lymphoblastoid cells (Gentest
    cDNA microsomes) using fluorescent probes has been evaluated using 68 marketed drugs. In general lower IC50 values were obtained with Cypex bactosomes compared with Gentest cDNA microsomes. This could be due to use of higher concentration of protein and also the lower activity of Gentest cDNA microsomes. Notably, when compared with in vivo clinical drug-drug interactions (cDDIs) gathered from clinical studies reported in the scientific literature Cypex bactosome data was better at predicting in vivo cDDI. Consequently, from the data obtained in this comparative study, a fluorescence based assay using Cypex bactosomes is more suitable as a front-line screen for the prediction of potential downstream CYP450 driven cDDIs.
    Original languageEnglish
    Pages (from-to)30-39
    Number of pages10
    JournalDrug Metabolism Letters
    Volume5
    Issue number1
    DOIs
    Publication statusPublished - 2012

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