Researchers at the University of Basel have developed a technique that allows them to simultaneously examine the effects of over 1500 active compounds on cell metabolism. This groundbreaking analysis has also unearthed new mechanisms behind well-known medications. This method could assist scientists in anticipating side effects and identifying extra uses for currently available drugs.
Researchers at the University of Basel have developed a technique that allows them to simultaneously examine the effects of over 1500 active compounds on cell metabolism. This groundbreaking analysis has also unearthed new mechanisms behind well-known medications. This method could assist scientists in anticipating side effects and identifying extra uses for currently available drugs.
How do active substances influence metabolic processes within cells? Finding the answer to this question could provide essential insights for creating new treatments. Previously, studying the effects of such substances across an entire compound library would have been incredibly resource-intensive.
Researchers from the Department of Biomedicine at the University of Basel have recently introduced a technique to evaluate the metabolic impacts of thousands of active compounds at once. They published their findings on this method, called high-throughput metabolomics, in the scientific journal Nature Biotechnology.
Predicting side effects and interactions
“By gaining a clearer understanding of how active compounds affect cell metabolism, we can speed up the drug development process,” states Professor Mattia Zampieri. “Our method offers deeper insights into these substances, helping us predict potential side effects or drug interactions.”
The research team, led by Dr. Laurentz Schuhknecht, who is the study’s lead author, cultured cells in numerous tiny wells on cell culture plates. They treated each well with one of the over 1500 substances from their compound library and employed mass spectrometry to observe how thousands of small molecules within the cells (known as metabolites) alter following treatment.
This enabled the team to collect data on the metabolic changes of over 2000 products within the cells for each active compound examined. They then evaluated these changes against those from untreated cells using computer-based analysis, resulting in a comprehensive overview of the impact of each substance on cell metabolism, providing accurate insights into its mode of action.
New applications for established medications
“Available drugs can affect cell metabolism far more significantly than we previously understood,” summarizes Zampieri, reflecting on the experimental outcomes. Particularly notable was the discovery of previously unrecognized mechanisms of common medications. For example, the team found that tiratricol, a drug for a rare thyroid disorder, not only acts primarily in its main role but also affects the production of certain nucleotides, which are vital for DNA synthesis.
“As a result, this medication could serve as a promising candidate for a new application: modulating nucleotide biosynthesis, making it potentially useful in cancer treatment to help slow down tumor growth,” adds Schuhknecht.
The extensive data obtained through high-throughput methods can facilitate the training of artificial intelligence aimed at designing novel drugs. “Our long-term goal is to align disease-specific metabolic profiles with the metabolic intervention modes of thousands of compound candidates to identify the most suitable medication that can reverse the molecular alterations caused by the disease,” states Zampieri.
To approach this vision, understanding how substances act on metabolism is crucial, the pharmacologist emphasizes. Equally important is understanding how the human body metabolizes these compounds and how that alters their effects. Therefore, the researchers are continuing their investigations to explore the interaction between the body and active substances in greater detail.
