Lead Optimization

These in vitro assays help you understand the potential stability of your compound in vivo. We use liver microsomes from mice, rats, dogs, monkeys, and humans to compute disappearance rates and predict in vivo clearance.

Metabolites are identified with Mass Spectrometry (LC-MS/MS), using various scan modes and fragmentation pathways of the compound. This information can guide the synthetic optimization of lead compounds by delineating the metabolic “soft-spots”.

We identify the CYP enzymes involved in the metabolism of lead compounds to aid prediction of drug-drug interactions. We also use FDA recommended inhibitors and recombinant CYP enzymes for confirmation. 

In vitro induction of cytochrome P450 (CYP) enzymes is an important predictor of drug-drug interactions. We use real time PCR assays for CYP expression and can test enzymatic activity of induced CYP to understand your compounds potential for clinical drug-drug interactions. 

The extent of drug distribution, metabolism and elimination is dependent on the amount of free compound in systemic circulation. We use in vitro assays such as equilibrium dialysis and ultrafiltration to help you understand the species-specific plasma protein-binding. 

Concentrations of drugs may differ between plasma and whole blood as a consequence of different binding to specific cells. We use a well-established assay to define the blood to plasma ratio that is important for predicting whole body pharmacokinetics.