DNA-Encoded Library in Drug Discovery with Massive Data Production
발표자
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초록
내용
The importance of a new screening platform for deriving lead substances in new drug development has always been clear, wherein the screening of hundreds of thousands of compound libraries in small-molecule drug development is considered the starting point for determining the success of new drug development. However, to construct the high-throughput screening (HTS) system for screening a large number of compounds, there are many financial and spatial limitations depending on the size and type of the library. To overcome this, DNA is used as a barcode through its conjugation with small-molecule compounds. As a result, the DNA-encoded library technology, which enables rapid assays to be carried out, began to emerge. This technology, which was conceptually proposed by Brenner and Lerner in 1992, has undergone a long period of improvement and is now being used by many pharmaceutical companies together with HTS, to derive various new drug candidates. For examples, RIPK1 and sEH targeted small-molecule inhibitors developed by GSK during clinical trials were selected via the chemical modification of hit compounds obtained from a DNA-encoded library screening. However, existing synthetic methods for constructing DNA-encoded libraries are limited. In this report, a procedure for synthesizing N-acylsulfonamide functional groups applicable to DEL construction was developed in the presence of a copper reagent and water as a nucleophile from simple alkynes or sulfonyl azides, which are widely commercially available. Furthermore, we prove that a new alternative procedure can be used to construct a DNA-encoded library.