Since their initial conception concept was conceived in 1992 (Brenner, S., Lerner, R. A. Proc. Natl. Acad. Sci. 1992, 89, 5381-5383), DNA-encoded chemical libraries (DEL) have evolved into a valuable platform for hit identification in early drug discovery. Compounds in DELs consist of building blocks serving as diversity elements, which are encoded by unique DNA sequences as identification “barcodes,” and are assembled combinatorially in split-and-pool fashion via DNA-compatible reactions.
The DEL technology enables the fast and economic synthesis, screening and analysis of DNA-encoded collections of millions to billions of compounds against biological targets through a confluence of molecular biology, combinatorial chemistry, high throughput sequencing and advanced informatics techniques. Compared to traditional high-throughput screening (HTS), DEL possesses multiple merits, including a much larger library size and more cost-efficient affinity screens. HitGen has been building a large collection of novel, diverse and drug-like DELs as its primary drug discovery platform.