DMPK
The Aim of the DMPK core is to support proof-of-concept (POC) probe development with quantitative stability, metabolism and pharmacokinetic data. Potent and selective POC chemical probes with the distributional properties and stability necessary for use in whole animal pharmacology systems is the highest standard of probe that a Center can generate. Compounds identified by the initial screens as potential probes are likely to require additional optimization of affinity and specificity to be useful in vitro research tools; however, additional factors must be optimized to generate a high quality in vivo probe. In addition to selective target binding, a successful in vitro probe molecule must reach the target tissue at sufficient concentrations to elicit the desired biological effect. In addition to pharmacokinetic considerations, several pharmacodynamic factors as plasma protein binding, solubility, and permeability will influence the ultimate efficacy of any derived biological probes. Depending on the objectives of the probe development project, probe compounds are evaluated in the following assays; Plasma Protein Binding, solubility cytochrome P450 inhibition, plasma and hepatic microsomal stability.
