In this HOT perspective, Hasselgreen and co-workers at AstraZeneca R&D Mölndal, reflect on the tough crisis that has afflicted the pharmaceutical industry in recent years, where the increased R&D budgets have not translated into new valuable products. This review offers an excellent overview of aspects and practicalities involved in preclinical toxicity prediction and analysis. The authors inspect commonly used guidelines/rules in medicinal chemistry aimed at reducing toxicity wondering if a simple distinction between compounds that have safety liabilities and “clean” compounds really exists. And crucially, they reflect on the impact of applying such guidelines on compounds progressing to clinical phases or even further and becoming approved drugs.
A critical assessment of modeling safety-related drug attrition
Daniel Muthas, Scott Boyer and Catrin Hasselgren
DOI: 10.1039/C3MD00072A
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