Having had vast experience in the preclinical drug discovery process, we understand the important of lead optimization that takes into account criteria other than potency and selectivity. For faster lead to candidate selection, we have incorporated metabolism assays that could identify potential pitfalls in the selection of certain functional groups and/or active metabolite formation that might be problematic at end stages of the game.
We offer services in the following areas:
- An extensive battery of in vitro P450 capabilities to both in-house hit-to lead as well as external singleton compounds.
- Based on in vitro assay results, we optimize analogs to dial out P450 liabilities (inhibition and/or induction) to avoid potential drug-drug interaction in the clinic.
- Provide interspecies P450 correlation data to help identify metabolites that might be unique to a specific species; this could be followed by scale up of the said metabolite if desired.
- Provide services for the synthesis of stable isotopically labeled analogs for the quantification of potentially toxic metabolites produced on bioactivation by P450’s.
- Provide MDCK/Caco-2 assays to evaluate permeability aspects in the process of refining the selection of analogs that progress intoin vivo pharmacokinetics.
- Provide mutagenicity assays for advanced lead molecules or late stage analogs.