Designing drugs without heart side-effects

Drug induced hERG potassium channel inhibition: Novel access and binding determinants?

The heart’s ability to pump blood depends on co-ordinated electrical activity generated by molecules in heart cells called ‘ion channels’. One of these channels is called hERG, and is essential for normal heart function. However, many drugs used to treat disorders with no relation to heart disease can affect hERG’s function. This can cause side effects such as abnormal heart rhythms, which can have fatal consequences. In this project, Professor Jules Hancox is looking for ways to design drugs that do not have hERG-related side effects. To do this, they need to understand precisely how different drugs interact with hERG. In many cases, these side effects are the result the drugs affecting the central ‘pore’ of hERG channel, where the ions (e.g. calcium, potassium) enter and exit. However it is not always the case, as drugs might also be able to interact with hERG at other levels. Previous studies have shed light on the detailed structure of this central ‘pore’. In this project, Professor Hancox and his team intend to use computational models, combined with experiments in the lab, to investigate whether drugs can interact with hERG in ways different to those currently known. This could provide alternative routes for drug design that would eliminate adverse reactions seen with current drugs.