Follow-up Studies

Follow-up Studies offered by Sekisui XenoTech's Enzyme Inhibition Group

Direct Inhibition

Ki determinations: Determine Ki value for direct inhibition with multiple concentrations of the drug candidate and marker substrate.

Metabolism-Dependent Inhibition (MDI)

1. XTRA (XenoTech Reversibility Assay): Our unique approach utilizes ultracentrifugation to determine the mechanism associated with metabolism-dependent inhibition. This assay determines if the metabolism-dependent inhibition is due to:
- formation of a more potent reversible inhibitory metabolite
- formation of a quasi-irreversible metabolite inhibitor complex (MIC formation)
- irreversible inactivation (indicates possible covalent binding)

2. MIC Formation: evaluation of a drug candidate for spectral changes associated with metabolite inhibitory complex formation.

3. KI and kinact determinations: Determine KI and kinact values for the inactivation of an enzyme by a drug candidate using multiple drug concentrations and preincubation time points.
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