Drug Discovery Core

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DRUG DISCOVERY CORE – ABSTRACT The Drug Discovery Core will support all project teams to identify hits, convert them to tool compounds, leads and eventually development candidates for preclinical profiling. More specifically, we will rely on existing chemical matter (compound archive, commercial sources) and expertise at Novartis to optimize compound collections for screening purposes. Our extensive experience of using a suite of computational approaches, including machine learning and artificial intelligence, will allow us to improve hit rates and therefore obtaining hits more rapidly with fewer compounds being screened without compromising on chemical diversity. The identified hits, resulting from a collaborative effort with High-Throughput Biology Core, will be validated and further progressed towards tool and lead compounds by improving potency and selectivity and initiating a multi-parameter optimization at an early stage to achieve drug-like properties of lead and development compounds. Additional parameters of particular importance include in vitro and in vivo metabolic stability in multiple species, lipophilicity, solubility, plasma protein binding, permeability, and oral bioavailability. Projects with known targets will be supported by structure-based drug design (SBDD) and computational tools that cannot only add another dimension for compound design but will also allow the identification of structurally different chemical matter with similar properties (scaffold hopping) to add diversity and improve chances of success. As compounds enter the lead optimization stage and further advance towards development candidates, we will increasingly collaborate with the Translational Research Core to examine the in vivo pharmacokinetic behavior of advanced leads, better understand their potential for off-target activities, and examine their behavior in dose- range finding toxicity studies. At this stage, the Virology Core will examine compounds in relevant animal models for efficacy and pharmacodynamics and its main parameters driving it. This information is key to allow a decent human dose prediction that is important to assess a compound’s potential to become a successful drug. In summary, the Drug Discovery Core will – together with the other Cores – provide the infrastructure, resources, and expertise to identify hits, convert them to tool and lead compounds and optimize them to multiple, high quality development candidates with the goal to deliver 3 IND and 3 additional Development Candidates.