New single-molecule tracking system accelerates drug discovery process
A new automated screening technology developed by Japanese researchers enables rapid identification of drug candidates by tracking molecular behaviour within cells, offering significant implications for therapeutic development.
Researchers at Osaka University have developed an innovative drug screening method that could substantially accelerate the drug discovery process. The technique, which employs single-molecule tracking technology, has demonstrated remarkable efficiency in identifying both known and previously unknown drug interactions with cellular targets.
Technical advancement
The newly developed system, known as AiSIS (Automated in-cell Single-molecule Imaging System), represents a significant technical advancement in drug screening methodology. The system’s capability to track individual molecules within cells provides unprecedented insight into drug-target interactions at a molecular level. According to the research published in Nature Communications on 31 October 2024 [1], the technology performs screening procedures approximately 100 times faster than conventional manual methods.
The research team, led by Daisuke Watanabe, validated their screening approach using the epidermal growth factor receptor (EGFR), a well-established therapeutic target in oncology. EGFR was selected due to its crucial role in cancer development and progression, particularly in lung cancer, where several EGFR-targeting drugs are already in clinical use.
The validation process involved screening a library of more than 1,000 approved drugs. “We successfully identified all the drugs that are known to target EGFR and are currently used to treat cancer patients,” explained Watanabe. “More importantly, we found that the library included seven drugs that until now were not known to affect EGFR.”
Molecular behaviour insights
A key feature of the new technology is its ability to visualise molecular behaviour in real-time. The system can observe and analyse changes in target molecules’ assembly and disassembly patterns following drug treatment, a process known as multimer formation. This capability provides valuable insights into drug mechanisms that were previously difficult to obtain.
Senior author Masahiro Ueda emphasises the novelty of their approach: “Screening using single-molecule imaging provides a new means to discover drugs by observing the movement of biomolecules in cells and the formation of multimers. This has not been used for drug discovery until now, and it means we should be able to develop new drugs with different mechanisms of action and even repurpose already approved drugs to new targets.”
Future applications
The successful validation of this screening method using EGFR as a target opens up possibilities for investigating other receptor targets involved in disease development and progression. The technology’s ability to rapidly screen large numbers of compounds while providing detailed molecular interaction data could prove particularly valuable in identifying new therapeutic applications for existing drugs. The system’s capacity to observe molecular behaviour in cellular environments offers a more comprehensive understanding of drug-target interactions compared to traditional screening methods. This enhanced insight could potentially lead to more effective drug development strategies and reduce the time required to identify promising therapeutic candidates.
Implications for drug development
The development of this screening technology represents a significant step forward in drug discovery methodology. By combining highthroughput screening capabilities with detailed molecular interaction analysis, the system offers a more efficient and informative approach to identifying potential therapeutic compounds.
The ability to repurpose existing drugs for new therapeutic applications is particularly significant, as this approach could substantially reduce the time and cost associated with bringing new treatments to patients. The identification of seven previously unknown EGFRinteracting drugs from the approved drug library demonstrates the potential for discovering new applications for existing pharmaceuticals.
Reference:
1. Watanabe, D., Hiroshima, M., Yasui, M., & Ueda, M. (2024). Single molecule tracking based drug screening. Nature Communications, 15, 8975. https://doi.org/10.1038/s41467-024-53432-w
Drug screening with automated system for in-cell single-molecule imaging. (Bottom) Diffusion coefficient of the receptor (left) and cluster formation (right) were measured from 1,000 cells. These distributions obtained by every cell changed with EGF stimulation. (CC BY-NC-SA, 2024 Ueda et al., Single molecule tracking based drug screening. Nature Communications)
