Rapid Late-Stage Lead Optimization

Rapid Late-Stage Lead Optimization Overview

Pharmaron’s rapid late-stage lead optimization service produces data that can play a vital role in making swift, affordable decisions around selecting and advancing the right lead candidate(s) prior to initiating IND-enabling toxicology studies. This cost-effective solution provides these data within a few weeks. 

Pharmaron has combined our expertise in tritiation with our in vivo/in vitro drug metabolism capabilities to generate both QWBA tissue distribution and in vitro cross-species comparative metabolism data, which can assist with selection of toxicology species, provide an early insight into a compound’s distribution and metabolism and help with translational sciences bridging non-clinical with clinical investigations.

in vivo Tissue Distribution

• From ³H radiolabelling of test compounds to QWBA images/data in 2-3 weeks (for testing 5 compounds in parallel)
• Provides tissue distribution data for ³H radioactivity in up to 40 selectable tissues in rodents
• Comparison of distribution of total [³H] radioactivity (parent and/or metabolites) in key tissues with basic quantification of blood:tissue ratios which indicates if radiolabelled drug-derived material is moving from the blood into the tissues
• Key comparative target-distribution data for a panel of closely related compounds e.g. confirm if test compound(s) is reaching desired tissues or accumulating in sensitive tissues

in vitro Metabolism

• Target turnaround of 2-weeks from incubation to ³H metabolite profiles
• in vitro quantitative comparison of metabolites formed in hepatocytes from human vs. non-clinical species (e.g. mouse, rat. dog, minipig, monkey, human)
• Helps select most metabolically relevant toxicology species
• in vitro quantitative comparison of metabolites formed in hepatocytes from human vs. non-clinical species provides early indicative data on metabolite safety issues
• Identify formation of potential human-specific metabolites early
• Structural identification of metabolites by HRMS can be included (additional time required for Met ID)