Medchem Concepts – hERG, what is it and how to design it out?

hERG, or human Ether-à-go-go-Related Gene, encodes for a potassium ion channel in the heart. This channel is responsible for regulating the flow of potassium ions across cell membranes, which plays a crucial role in controlling the electrical activity of the heart. 

hERG channels are particularly important in drug discovery and development because certain drugs have the potential to block these channels. This can lead prolonged QT interval and increase the risk of a type of irregular heartbeat known as torsades de pointes, which can be fatal to patients. It is therefore essential to assess whether new compounds have the potential to block hERG and risk of causing cardiac arrhythmias early in the drug discovery process.

We offer hERG testing as part of our in vitro ADMET services. If a compound or a chemical series is found to block hERG channels, key drivers and structure activity relationship associated with it are identified by our drug hunters. Our medicinal chemistry experts use this data to deploy adapted strategies reducing hERG inhibition whilst maintaining high target potency and favourable ADMET parameters. Drugs with enhanced selectivity for their biological target over hERG reduce the risks of clinical attrition and provide safer drug for patients.

Download our brochure here to find out how medicinal chemistry strategies we use as part of our medicinal chemistry services to design out hERG inhibition.