Predictive in vitro toxicology screening to guide chemical design in drug discovery

The safety profile of a novel drug candidate is highly determinant of its chance of success to be launched for treatment of patients. The integration of predictive toxicology in the drug discovery process is essential to identify and mitigate potential safety issues in a timely manner and contributes to improved productivity in pharmaceutical R&D, especially for small molecules, which is the focus of this review. A range of predictive in vitro toxicology assays has been established, which we use as part of AstraZeneca's proactive discovery safety screening strategy, with the aim to influence chemical design and obtain candidate drugs with the right safety profile. Here, we discuss recent progress in some of the main areas of toxicity, such as cardiotoxicity, hepatotoxicity, CNS toxicity, genetic toxicity, and nephrotoxicity, and also considerations around assay validation, predictivity, and throughput, which are relevant to secure actual impact on drug design. Finally, we share our perspectives on future opportunities and innovation.