Small Targeted Cytotoxics: Current State and Promises from DNA-Encoded Chemical Libraries

Authors

  • Nikolaus Krall,

    1. Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Wolfgang-Pauli-Strasse 10, CH-8093 Zürich (Switzerland)
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  • Dr. Jörg Scheuermann,

    1. Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Wolfgang-Pauli-Strasse 10, CH-8093 Zürich (Switzerland)
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  • Prof. Dario Neri

    Corresponding author
    1. Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Wolfgang-Pauli-Strasse 10, CH-8093 Zürich (Switzerland)
    • Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Wolfgang-Pauli-Strasse 10, CH-8093 Zürich (Switzerland)
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Abstract

The targeted delivery of potent cytotoxic agents has emerged as a promising strategy for the treatment of cancer and other serious conditions. Traditionally, antibodies against markers of disease have been used as drug-delivery vehicles. More recently, lower molecular weight ligands have been proposed for the generation of a novel class of targeted cytotoxics with improved properties. Advances in this field crucially rely on efficient methods for the identification and optimization of organic molecules capable of high-affinity binding and selective recognition of target proteins. The advent of DNA-encoded chemical libraries allows the construction and screening of compound collections of unprecedented size. In this Review, we survey developments in the field of small ligand-based targeted cytotoxics and show how innovative library technologies will help develop the drugs of the future.

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