Referenced in: none

Automatically associated channels: Kv11.1

Title: Computational design and discovery of "minimally structured" hERG blockers.

Authors: Andrea Cavalli, Rosa Buonfiglio, Cristina Ianni, Matteo Masetti, Luisa Ceccarini, Rachel Caves, Michael W Y Chang, John S Mitcheson, Marinella Roberti, Maurizio Recanatini

Journal, date & volume: J. Med. Chem., 2012 Apr 26 , 55, 4010-4

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22455383

Abstract
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.