Tox-Database.net: a curated resource for data describing chemical triggered in vitro cardiac ion channels inhibition

The aim of this database development and publication was to provide a scientifically useful, easily usable and clearly verifiable set of information describing not only IKr (hERG), but also other human cardiomyocyte specific ionic channels inhibition data (IKs, INa, ICa).The broad range of data (chemical space and in vitro settings) and the easy to use user interface makes tox-database.net a useful tool for interested scientists.http://tox-database.net. webciteDrug development is a time and resource consuming process with multiple potential obstacles. Until very recently pharmacokinetic and biopharmaceutical issues were recognized as being the major obstacles, although due to new approaches and tools they were mostly bypassed [1]. Drug safety and toxicity issues are now recognized as being factors generating the most reasons for drug withdrawals at various levels of development and at the post-approval stage. The latter one remains especially harmful as the costs include not only financial, but also a population health burden [2,3]. In recent years much regulatory, industry and public attention has been focused especially on cardiotoxicity. This due to the leading position of cardiotoxicity among the reasons for drug withdrawals, relabeling and late attritions. QT prolongation and potentially fatal arrhythmia, torsade de pointes, occurrence are the most pronounced manifestations of a drugs’ cardiac toxic effects, thus evaluation of the proarrhythmic potential of an investigated compounds is now an integral element of the safety profile required for the approval of new drugs. For all drugs with a proven proarrhythmic activity the capacity to inhibit the rapid delayed rectifier potassium current, IKr, carried by the membrane channel which is composed of subunits encoded by the human ether-à-go-go related gene (hERG) was recognized as being an underlying mechanism of such an effect. However, it has been suggested that the hERG blocking potency, defined as a compound co