Objective
During the optimisation of lead compounds for the delivery of novel drug candidates, improvement of compound efficacy and safety are key objectives. However, some of the adverse events related to drug metabolism, transport, drug-drug interactions and drug clearance are typically not identified until much later in drug development. Drug induced liver injury (DILI) is a major contributor to the attrition of novel compounds during development. Unacceptable safety was highlighted as the primary cause for project closures during preclinical and phase I drug development, with the liver toxicity a major factor (Kramer 2007; Cook, 2014).
We have worked to develop a number of improved cell-based assays and predictive models to enable project-tailored screening cascades to assess liver safety profiles, with an emphasis on fail fast or fail early, facilitating more efficient and effective drug discovery. We herein present a number of screening assays utilising both 2D and 3D cell culture platforms which we employ to assess drug induced liver injury (DILI). These assays enable our clients to make informed decisions and make progress towards identifying the right molecule to progress towards the clinic. We also show a number of assays and techniques currently under evaluation in our discovery toxicology service portfolio.
