Experimentally Validated hERG Pharmacophore Models as Cardiotoxicity Prediction Tools Jadel M. Kratz Daniela Schuster Michael Edtbauer Priyanka Saxena Christina E. Mair Julia Kirchebner Barbara Matuszczak Igor Baburin Steffen Hering Judith M. Rollinger 10.1021/ci5001955.s001 https://acs.figshare.com/articles/journal_contribution/Experimentally_Validated_hERG_Pharmacophore_Models_as_Cardiotoxicity_Prediction_Tools/2241511 The goal of this study was to design, experimentally validate, and apply a virtual screening workflow to identify novel hERG channel blockers. The hERG channel is an important antitarget in drug development since cardiotoxic risks remain as a major cause of attrition. A ligand-based pharmacophore model collection was developed and theoretically validated. The seven most complementary and suitable models were used for virtual screening of in-house and commercially available compound libraries. From the hit lists, 50 compounds were selected for experimental validation through bioactivity assessment using patch clamp techniques. Twenty compounds inhibited hERG channels expressed in HEK 293 cells with IC<sub>50</sub> values ranging from 0.13 to 2.77 μM, attesting to the suitability of the models as cardiotoxicity prediction tools in a preclinical stage. 2014-10-27 00:00:00 screening workflow 2.77 μ M bioactivity assessment 50 compounds IC 50 values Cardiotoxicity Prediction ToolsThe goal HEK 293 cells hERG channel novel hERG channel blockers drug development cardiotoxicity prediction tools cardiotoxic risks model compound libraries hERG channels Validated hERG Pharmacophore Models