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Cyprotex Extends Cloe® Screen Mechanism-Based Inhibition Service to Include 4 Additional Cytochrome P450 Isoforms

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Cyprotex announces that it has enhanced its Cloe® Screen Mechanism-Based Inhibition service to include 4 additional cytochrome P450 (CYP450) isoforms.

These new assays compliment the CYP3A4 isoform assay which was launched last year, and provide information on 5 of the major CYP450 isoforms which are of interest in drug discovery.

The inhibition of human CYP450s is one of the most common mechanisms that can lead to drug-drug interactions. Metabolic drug-drug interactions, following the co-administration of drugs, can result in either reduced efficacy or increased toxicity.

In early drug discovery it is critical to select candidates with a minimum potential of inhibition of CYP450 in order to avoid late stage issues or failures.

The consequences of mechanism-based CYP450 inhibition are considered to be more serious than reversible inhibition because the inactivated enzyme must be re-synthesised before activity is restored.

Within the Pharmaceutical Industry, the importance of identifying compounds which are mechanism-based inhibitors at an early stage of drug discovery is now being recognised.

This has been further intensified by the release of the draft FDA regulatory guidelines on drug interactions which recommend that mechanism-based inhibition is investigated using in vitro screening protocols. The assays have been designed using probe substrates which are advocated by the draft FDA guidelines.

Dr. Darwin Cheney, Cyprotex's Chief Scientific Officer, comments on the launch of this new service. "We have developed these additional mechanism-based inhibition assays in response to both customer demand and regulatory guidelines. The prevalence and clinical implications of mechanism-based CYP450 inhibition has placed greater emphasis on the early detection of compounds with this potential."