Rapid metabolism is a major limiting feature of many new drug candidates. It can lead to low oral bioavailability, a short in vivo half-life or the production of potentially active or toxic metabolites.
CDCO offers a range of standard and custom-designed assays to assess the metabolism of compounds during lead optimisation and preclinical development.
Metabolite characterisation studies are performed to:
- identify major metabolic products and metabolising enzymes of a test compound
- identify metabolically labile functional moieties within a structural series
- provide a basis for structural modifications to reduce metabolic liabilities
Research platforms include:
- metabolic stability using liver microsomes or cryopreserved hepatocytes
- metabolite identification and characterisation
- species comparisons of metabolite profiles
- CYP and UGT reaction phenotyping
- stability in blood and/or plasma
- stability in gastric and intestinal fluids
- glutathione conjugate/reactive metabolite detection