Advancing small-molecule drug discovery by encoded dual-display technologies.

Trends Pharmacol Sci

ETH Zürich, Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Zürich, Switzerland. Electronic address:

Published: November 2023


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Article Abstract

DNA-encoded chemical library technology (DECL or DEL) has become an important pillar for small-molecule drug discovery. The technology rapidly identifies small-molecule hits for relevant target proteins at low cost and with a high success rate, including ligands for targeted protein degradation (TPD). More recently, the setup of DNA- or peptide nucleic acid (PNA)-encoded chemical libraries based on the simultaneous display of ligand pairs, termed dual-display, allows for more sophisticated applications which will be reviewed herein. Both stable and dynamic dual-display DEL technologies enable innovative affinity-based selection modalities, even on and in cells. Novel methods for a seamless conversion between single- and double-stranded library formats allow for even more versatility. We present the first candidates emerging from dual-display technologies and discuss the future potential of dual-display for drug discovery.

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http://dx.doi.org/10.1016/j.tips.2023.08.006DOI Listing

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