Discovery
Medicinal Chemistry Services
Discovery ADME
- Metabolic Stability
- CYP Interaction
- Permeability & Transporters
- Physicochemical Properties
- Protein Binding
Metabolite identification plays a key role in drug discovery, pre-clinical development, and clinical development. Metabolite ID studies are designed not only to screen metabolites, but these purpose-driven assays can also answer different questions. As the compounds progress through different stages, the goals and details of metabolite identification also change.
In early drug discovery, a metabolic stability assay is designed to identify compounds that are more resistant to metabolic turnover.
Frontage Laboratories offers rapid metabolite profiling services with approximately 3-5 days of turnaround time. Our scientists conduct metabolite identification studies to identify and confirm the site of metabolism and the corresponding structural moieties. This information greatly enhances the effectiveness of the metabolic stability assay and facilitates the selection of the next series of compounds.
At Frontage Labs, we provide assays generating both quantitative and qualitative data from metabolic stability and metabolite “softspot” experiments, respectively, using the same incubation samples. In addition, we can provide PK data and an in-vivo metabolite snapshot from plasma samples.
At Frontage, mass balance studies are designed using radiolabeled drugs to quantitatively track the fate of the drug and to determine the route of elimination, either through biliary or renal excretion, the two primary elimination routes for most drugs.
CYP450 reaction phenotyping determines which CYP isoform is responsible for generating which metabolite. These data, in conjunction with the excretion data from a mass balance study, are important in designing future drug-drug interaction studies.
Both the FDA and ICH have issued guidelines requiring assessment of the abundance of circulating human metabolites and providing proof that these same metabolites are also observed circulating in the safety species at an equivalent or greater abundance. Our team can conduct studies to determine if additional toxicity studies of specific metabolites are needed.
Data on the routes of excretion and the structures of observed metabolites are required for final drug approval. These data are obtained by dosing human subjects with a radio-tracer and determining which metabolites are eliminated via the urine or feces.
This service can help to address the goals of both in vivo pharmacokinetics (PK) screening and metabolite profiling early, rapidly, and economically. The unique feature of this service is to integrate previously unrelated DMPK studies into one lab, using one animal study, one analytical instrument, and one study team.