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

被引:14
作者
Polak, Sebastian [1 ]
Wisniowska, Barbara [1 ]
Glinka, Anna [1 ]
Polak, Milosz [1 ]
机构
[1] Jagiellonian Univ, Coll Med, Fac Pharm, Unit Pharmacoepidemiol & Pharmacoecon, PL-30688 Krakow, Poland
关键词
In vitro data; Cardiotoxicity; Sodium current; Slow potassium current; Rapid potassium current; L-type calcium current; IC50; QT-INTERVAL; COMMON POLYMORPHISM; DEATH-SYNDROME; GENE VARIANTS; HERG; KCNH2; SCN5A; KCNQ1; KCNE1; MUTATIONS;
D O I
10.1186/2050-6511-13-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: Drugs safety 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. Among them cardiotoxicity remains the main reason, despite the substantial effort put into in vitro and in vivo testing, with the main focus put on hERG channel inhibition as the hypothesized surrogate of drug proarrhythmic potency. The large interest in the IKr current has resulted in the development of predictive tools and informative databases describing a drug's susceptibility to interactions with the hERG channel, although there are no similar, publicly available sets of data describing other ionic currents driven by the human cardiomyocyte ionic channels, which are recognized as an overlooked drug safety target. Discussion: 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). Summary: 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.
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页数:13
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