Computational design and discovery of 'minimally structured' hERG blockers

摘要

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.