Advantages of performing hERG screening early in the drug discovery process
Early hERG screening provides significant benefits in the drug discovery and development process by enabling more informed decision-making and efficient use of resources. Early identification of potential cardiac liabilities helps to avoid costly late-stage failures, streamline development timelines, and improve the overall safety profile of drug candidates. By conducting hERG screening at an early, non-GLP (Good Laboratory Practice) stage, pharmaceutical companies can enhance the efficiency and success rate of their drug development pipelines. The key advantages of early hERG screening include:
Early risk identification
Non-GLP hERG screening allows researchers to identify potential cardiac liabilities of drug candidates at an early stage of development. By detecting these issues early, problematic compounds can be eliminated before significant resources are allocated to their development. This early intervention minimises the risk of late-stage failures, which are often costly and time-consuming. Furthermore, early identification allows researchers to prioritise safer candidates and focus resources on optimising their profiles.
Cost efficiency
Conducting hERG screening in a non-GLP environment is considerably more cost-effective than GLP-compliant studies. Early-stage non-GLP screening helps manage research and development budgets more effectively by allowing companies to screen large numbers of compounds at a lower cost. Additionally, reducing the number of compounds that advance to expensive GLP studies reduces overall development costs.
Rapid turnaround
Non-GLP hERG screening is typically faster than GLP studies, as it involves fewer regulatory requirements and procedural complexities. This rapid turnaround time is essential during the early stages of drug discovery, where quick decision-making can significantly impact the overall timeline. Quick feedback also provides medicinal chemists with valuable information for adjusting compound structures and improving safety profiles without causing delays.
High-throughput Capability
Non-GLP hERG screening often relies on automated patch clamp systems and other high-throughput technologies, allowing for the simultaneous testing of large numbers of compounds. This high-throughput capacity enables researchers to screen hundreds to thousands of compounds within a short period, which is particularly beneficial during the early discovery phase when multiple candidates are being evaluated. The ability to rapidly assess the cardiac safety of numerous compounds increases the likelihood of identifying viable leads while reducing the time and cost associated with manual or lower-throughput methods. This approach also enables more comprehensive data generation, facilitating better-informed decision-making.
Optimisation of lead compounds
Early identification of hERG liabilities provides medicinal chemists with critical information for optimising lead compounds. If a compound exhibits hERG-related issues, researchers can modify its chemical structure to reduce or eliminate hERG inhibition while retaining its therapeutic activity. This iterative process of optimisation can be conducted more efficiently in a non-GLP setting due to lower costs and faster turnaround times. By refining compounds early, researchers can enhance the safety and efficacy of drug candidates before advancing them to more rigorous and expensive GLP studies. This targeted approach improves the chances of success in later stages of development.
Strategic decision making
Data generated from early non-GLP hERG screening informs strategic decisions about which compounds to advance to more costly and time-consuming GLP studies. By filtering out candidates with poor hERG profiles early, pharmaceutical companies can allocate resources more effectively and focus on the most promising drug candidates. This strategic selection process reduces the likelihood of late-stage failures and increases the overall efficiency of the drug development pipeline. Early screening data also enables more accurate risk-benefit assessments, helping companies align their development strategies with regulatory expectations and market needs.
