The ADME/PK Laboratory and StarDrop teams have worked with a number of customers applying both StarDrop and experimenal ADME technologies to their projects. The following case studies demonstrate different ways in which our expertise has been utilized sucessfully to achieve the desired project results.

Case Study 1: Reducing synthesis cycles in lead optimization

The ADME/PK Laboratory was asked to help a client with a difficult project to identify an orally bioavailable therapy for a CNS target. To date, they had not identified an active compound that had an acceptable combination of both oral bioavailability and CNS penetration. The client provided all project data and wanted to know how StarDrop could have helped them to identify suitable compounds at an earlier stage and how much resource its application would have saved.

Following initial screening of over 3,000 compounds selected from a virtual library of over 13,000 molecules, a client identified multiple hits across 13 different chemistries. Due to resource limitations, the project team had to decide where to focus their synthetic effort in order to maximize the probability of identifying chemistries that would yield tractable lead series.

In vitro potency, selectivity, solubility and microsomal stability data had been generated for a set of 150 client compounds. Compounds had previously been selected for in vivo study based on selectivity and potency, ignoring potential solubility and metabolic stability problems and resulting in poor bioavailability in rats. We were asked to select compounds with a balanced set of properties for progression in vivo using our proprietary prioritization suite.

The ambitious target set by a client was to identify a novel drug candidate for a cardiac target and progress the chosen molecule to Phase I clinical trials within 2.5 years. Initial hits were obtained against the target and the chemistry program focused on a limited number of related chemotypes.