With a hit rate of ~30% observed across the industry (Brennan et al. 2024) hERG channels have a high off-target hit rate that has a well-documented link to life-threatening cardiac arrythmias including Torsade de Pointes. Therefore, screening of novel compounds is essential to eliminate this liability early, before lead development, where it becomes more challenging to address.

This early screening supports efficient resource allocation and informed decision-making, ultimately contributing to the successful development of safer drugs.

1. Early risk identification:  Non-GLP hERG screening helps identify potential cardiac liabilities of compounds early in the drug development process. This early identification allows for the elimination of problematic compounds before significant resources are invested in their development.
2. Cost efficiency:  Conducting hERG screening in a non-GLP environment is less expensive than GLP-compliant studies. Early-stage, cost-effective screening helps manage budgets more effectively, especially when dealing with a large number of compounds.
3. Rapid turnaround:  Non-GLP screening can be conducted more quickly than GLP studies. This rapid turnaround time is crucial for early-stage decision-making and helps accelerate the drug development process.
4. High-throughput: Non-GLP screening often utilize automated patch clamp systems, allowing for higher throughput screening. This efficiency is more cost effective and enables the assessment of many compounds in a short period. This strategy is particularly beneficial during the early discovery phase when numerous candidates are being evaluated.
5. Optimization of lead compounds: By identifying hERG liabilities early, researchers can modify lead compounds to mitigate these risks. This iterative process of optimization via medicinal chemistry efforts can be done more quickly and efficiently in a non-GLP setting.
6. Strategic decision making: Early non-GLP hERG screening data informs strategic decisions about which compounds to advance to more costly and time-consuming GLP studies. This strategic filtering ensures that only the most promising candidates proceed further.

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