Predicting drug interactions through metabolism assays
Syngene offers a complete suite of assays that analyze metabolism-based drug-drug interactions mediated primarily by the cytochrome P450 (CYP) superfamily of enzymes. These studies help clients analyze their drug candidate’s effect on the CYP450 enzyme and identify potential adverse reactions, thereby enhancing the safety and efficacy of the drug candidate. Our teams measure drug metabolism using both CYP inhibition and induction studies to understand drug exposure and reduce the attrition rate of compounds in later stages.
The CYP inhibition studies include reversible CYP inhibition assays that use discrete and pooled substrate approaches, and time-dependent inhibition assays that involve measuring the values for IC50, kobs (at low and high concentration), kinact/ KI, as well as performing studies on liver microsomes.
Our detailed analysis of CYP450 induction includes measuring mRNA levels, enzymatic activity, and cytotoxicity in hepatocytes using a non-destructive methodology. During the incubation process, we measure the levels of concentration in the test compounds and a pre-study helps us assess the solubility of compounds and non-specific binding to test systems.
Our range of assays include:
- Reversible cytochrome P450 inhibition
- Time-dependent inhibition
- Reaction phenotyping (CYP Identification)