Strategies for targeting undruggable targets

DNA-Compatible ortho-Phthalaldehyde (OPA)-Mediated 2-Substituted Isoindole Core Formation and Applications

“…DNA-encoded chemical library (DEL) has been proved to be a powerful tool in hit discovery and widely accepted in both the pharmaceutical industry and academia during recent years. , In a DEL, each synthetic chemotype (chemical compound) is covalently tethered with an identical encoding genotype (DNA tag), and the spatial encoding in traditional high throughput screening is replaced with DNA encoding, therefore allowing the biologically active ligand discovery process at a relatively low cost. − The high level of productivity of DEL in hit discovery has been confirmed by preclinical and clinical drug candidates ranging from kinase inhibitors to epigenetic modulators. − The success of DELs heavily relies on the collection of compounds with drug-like properties. ,− Therefore, the development of DNA-compatible synthetic methods to expand the chemical composition of DEL is highly desired. − Critically, several methodologies have been developed recently to generate drug-like moieties with the encoded DNA tag. − While medicinal chemistry research has continuously witnessed drug-like moieties demonstrating fascinating pharmacological activities, there are still limitations in the expansion of DNA-compatible reactions in pursuit of drug-like moieties …”

Visible Light-Promoted Divergent Benzoheterocyclization from Aldehydes for DNA-Encoded Chemical Libraries

“…Within 30 years of development, DNA-encoded chemical library (DEL) technology has proven to be a powerful tool in drug discovery, greatly facilitating hit discovery via affinity selection of compound collections against biotargets . The success of DEL technology largely relies on the chemical space and structural diversity of DNA-conjugated compounds, and consequently, developing DNA-compatible synthetic methods would allow the exploration of its potential .…”

DNA-Compatible Diversification of Indole π-Activated Alcohols via a Direct Dehydrative Coupling Strategy

“…DNA-encoded chemical libraries (DELs) technology combines the power of combinatorial synthetic chemistry with effective DNA barcoding methodology to offer a collection of millions of encoded chemical members . This technology has emerged as a valuable platform for drug discovery and has been widely adopted by academia and the pharmaceutical industry …”