PROTACs'Design of Tumor-targeting Inhibitors and Their Use in the Development of New Anti-tumor Drugs
Abnormal protein expression often leads directly or indirectly to the development of cancer.Currently,small-molecule inhibitors that target specific proteins are widely used in tumor therapy.However,small-molecule inhibitors have problems such as susceptibility to drug resistance,limited range of target proteins,and high toxicity,which limit their clinical application.As a result,proteolysis-targeting chimaera technology has emerged.Proteolysis targeting chimaeras(PROTACs)are a type of synthetic small-molecule compound consisting of target protein ligand,linker and E3 ubiquitin ligase ligand.It can use the human body's own ubiquitin-proteasome system(UPS)to ubiquitinate and degrade the target protein,which to some extent solves the problem of drug resistance caused by overuse of small-molecule inhibitors,and has the advantage of low toxicity.Therefore,this review has summarized the design and application of PROTACs developed by using existing small-molecule inhibitors in the field of cancer,based on the top five cancers with the highest incidence rate in China,with the aim of giving inspiration to new drug researchers,expanding the use of small-molecule targeted inhibitors,and breaking through the selection of drugs that are difficult to become drug sites.
Proteolysis-targeting chimaerasProtein degrationCancerUbiquitin-proteasome system
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