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Despite growing demand, the number of newly developed drugs has been steadily declining in recent decades. The search for new active substances, their production, their characterization and the detection of their biological effectiveness are very complex and expensive. One of the reasons is that the three steps have been carried out separately so far. Scientists at the Karlsruhe Institute of Technology (KIT) have successfully combined these processes on a chip, thus facilitating and speeding up procedures for producing promising substances. Thanks to miniaturization, the costs can also be reduced significantly. The results are now published in Nature Communications.
Drug development relies on high-throughput screening of large libraries of compounds. However, the lack of miniaturized and parallelized methodologies for high-throughput chemical synthesis in the liquid phase and the incompatibility of the synthesis of bioactive compounds and the search for their biological effect have led to a strict separation of these steps. This makes the process expensive and inefficient. "For this reason, we have developed a platform combining synthesis of compound libraries with high throughput biological screening on a single chip," says Maximilian Benz of the Institute of Toxicology and Genetics (ITG) of the KIT. This so-called chemBIOS platform is compatible with organic solvents for synthesis and aqueous solutions for biological screening. "We use the chemBIOS platform to perform 75 parallel three-component reactions for the synthesis of a lipid library, that is, fats, and then mbad spectroscopy characterization, the on-chip lipoplex formation and screening of biological cells ", adds Benz. Lipoplexes are nucleic acid-lipid complexes that can be absorbed by eukaryotic cells, that is, human and animal cells. "The whole process, from library synthesis to cell screening, takes only three days and about 1 ml of total solution, demonstrating the potential of chemBIOS technology to increase efficiency and effectiveness. to speed up screening and drug development, "says Benz. Usually, such methods require several liters of reagents, solvents and cell suspensions.
Recently, chemBIOS technology has been nominated for one of the top three places of the NEUTRAL Innovation Award of the 2019 KIT by a jury made up of representatives from research and industry.
Drug development: big efforts and few shots
Due to the enormous expense of time and the spatial and methodological separation of compound synthesis, screening and clinical studies, the development of new drugs often takes more than 20 years and costs between two and four billion dollars.
The initial phase of drug development is traditionally based on three scientific areas: chemists synthesize a large library of different molecules. All compounds are produced, isolated and characterized separately. Next, biologists badyze the library of molecules for biological activity. Highly active compounds, called hits, are returned to chemistry. On the basis of this screening, chemists synthesize other variants of these compounds. These libraries of secondary molecules then contain optimized compounds. After this cycle has been repeated several times, some promising candidate compounds are transferred to the medical part of the drug development, in which these compounds are tested in clinical studies. Over several thousands, then thousands of compounds subjected to a first screening, only one compound, if any, does not reach the final stage of drug development: the approval of the new drug. This process is time consuming and requires a wide range of materials and solvents. This makes development more expensive and slower and also limits the number of substances filtered to a reasonable number.
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Material provided by Karlsruher Institute for Technology (KIT). Note: Content can be changed for style and length.
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