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Development of High Throughput Assays for the Screening of Reversible and Mechanism-Based Cytochrome P450 Inhibition by Test Compounds

Abstract

Assessment of cytochrome P450 (CYP450) inhibition is now performed early in drug development to decrease thelikelihood of progressing a compound with the potential to cause drug-drug interactions.

Screening for reversible CYP450inhibition, which is widely performed, does not have the ability to detect mechanism-based inhibition of CYP450 by test compounds.The prevalence, and clinical implications, of mechanism-based CYP450 inhibition has placed greater emphasis on the early detectionof compounds with this potential.

We have developed and validated a high throughput reversible CYP450 inhibition assay using humanliver microsomes and industry recommended probe substrates.
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