Triazol: a privileged scaffold for proteolysis targeting chimeras.

Future Med Chem 2019 Nov 8;11(22):2919-2973. Epub 2019 Nov 8.

Henan Provincial Key Laboratory of Children's Genetics & Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou Children's Hospital, Zhengzhou University, Zhengzhou 450018, China.

Current traditional drugs such as enzyme inhibitors and receptor agonists/antagonists present inherent limitations due to occupancy-driven pharmacology as the mode of action. Proteolysis targeting chimeras (PROTACs) are composed of an E3 ligand, a connecting linker and a target protein ligand, and are an attractive approach to specifically knockdown-targeted proteins utilizing an event-driven mode of action. The length, hydrophilicity and rigidity of connecting linkers play important role in creating a successful PROTAC. Some PROTACs with a triazole linker have displayed promising anticancer activity. This review provides an overview of PROTACs with a triazole scaffold and discusses its structure-activity relationship. Important milestones in the development of PROTACs are addressed and a critical analysis of this drug discovery strategy is also presented.

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http://dx.doi.org/10.4155/fmc-2019-0159DOI Listing
November 2019

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