title: Small targeted cytotoxics: current state and promises from DNA-encoded chemical libraries.
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.
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Krall
authors.forename: Jörg
authors.initials: J
authors.lastname: Scheuermann
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
mesh_terms: D000906:Antibodies / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D010455:Peptides / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry*; D014815:Vitamins / Q000737:chemistry
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008024:Ligands; D010455:Peptides; D054852:Small Molecule Libraries; D014815:Vitamins; D004247:DNA