The study identifies minimal structural requirements for hERG blocking liability, which can help optimize lead compounds to eliminate potentially lethal side effects.
May guide hERG liability avoidance in lead optimization; leaves open clinical translation pending human validation.
Molecular knowledge of hERG blocking liability can offer the possibility of optimizing lead compounds in a way that eliminates potentially lethal side effects. In this study, we computationally designed, synthesized, and tested a small series of "minimally structured" molecules. Some of these compounds were remarkably potent against hERG (6, IC(50) = 2.4 nM), allowing us to identify the minimal structural requirements for hERG blocking liability.
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Cavalli et al. (2012) studied this question.
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