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.
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.
