Sygnature Discovery recently hosted a lecture by Professor Ruth Roberts and Dr Michael Morton from ApconiX. Based at BioCity in Nottingham, Sygnature Discovery is the UK’s largest independent provider of integrated drug discovery resource and expertise. The theme of the lecture and subsequent debate with the attendees was ‘Safety considerations in early chemical design: Challenges and opportunities’.
Ruth introduced the top of drug attrition. She explained that the reason most drugs fail pre-clinically is due to safety considerations, as opposed to a lack of efficacy or poor PK/PD. Top of the list is cardiovascular safety! To address this, the 3 key aspects of Target-Chemistry-Patient should be considered individually as part of the strategy to evaluate and mitigate risk. An important part of this is testing in vitro for unwanted ion channel activity. Mike explained how this activity can be measured, its translation in humans, and how this activity can be designed out by expert and timely collaboration with the chemist. The audience were keen to explore these ideas and the value of other in vitro assays as a basis for future collaboration as well as asking how this integrated approach might apply both to small molecules and to new modalities.