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Scientists at KIT are developing methods that simplify and accelerate chemical synthesis and biological drug screening by combining all steps on a single chip.
Source KIT : Despite rising demand, the number of newly developed drugs has been steadily declining in recent decades. The search for new active substances, their production, characterization and testing for biological effectiveness is very complicated and expensive. Partly due to the fact that all three steps were performed separately from each other. Scientists at the Karlsruhe Institute of Technology (KIT) have now been able to merge them into a single chip, significantly simplifying and accelerating the path to promising compounds. Thanks to the miniaturization, the costs can also be reduced considerably. The results were published by the team at Nature Communications (DOI 10.1038 / s41467-019-10685-0).
Drug development is based on the screening of large, high throughput drug libraries. However, as there are no miniaturized and parallelized methods at high productivity in the chemical synthesis in the liquid phase and at the same time the methods for the synthesis of bioactive compounds and screening for biological efficacy are generally not compatible, these steps are performed strictly separate. However, this makes the process expensive and inefficient. “So we have developed a platform with which we can combine the synthesis of whole-drug on-chip libraries with high-throughput biological exams,” said Maximilian Benz of the KIT Institute of Toxicology and Genetics (ITG).
The so-called chemBIOS platform is compatible with organic solvents for synthesis and aqueous solutions for biological screening. “We used the chemBIOS platform to perform 75 three-component parallel reactions to synthesize a lipid library, that is, fats, followed by its characterization by a mass spectrometry method, the formation of lipoplexes on the base-sliding platform and evaluation biological cell, “says Benz.
Lipoplexes are lipid-nucleic acid complexes that can be absorbed by eukaryotic cells, that is, between other human and animal cells. “The entire process from library synthesis to cell screening takes only three days and consumes about a milliliter of total solution, illustrating the potential of chemBIOS technology to increase efficiency and accelerate the screening and development of drugs, “Benz said. Normally, several liters of reagents, solvents and cell suspensions are used for such procedures.
The chemBIOS technology was recently nominated by a jury of research and industry representatives for one of the top three places in the KIT Innovation Award 2019.
Drug development: great effort and small success rate
Due to the immense amount of time and to the spatial and methodological separation of drug synthesis, the screening process and clinical trials, the development of a new drug usually takes more than 20 years and costs between $ 2 billion and $ 4 billion.
The early phase of drug development is traditionally based on three areas of science: chemists first synthesize a large library of different molecules. All compounds should be prepared individually, isolated and characterized. Subsequently, biologists study the molecular library for biological activity. Particularly active compounds, called “hits”, return to chemistry. Based on this pre-selection, chemists synthesize more variations of these compounds.
These secondary molecule libraries then contain optimized compounds. After a few rounds of this cycle, a small number of promising drug candidates are entering the medical area of drug development where these compounds are tested in clinical trials. Of several tens of thousands of compounds from the first screenings, only one, or none, reaches the final stage of drug discovery: drug approval for a new drug. This process is time consuming and requires a large amount of starting materials and solvents. All this makes development more expensive and slows down, limiting it to a viable number of active ingredients.
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