PROTAC: An Effective Targeted Protein Degradation Strategy for Cancer Therapy.

Wei-Dong Zhang,Zhi-Yuan Xu,Jinyun Dong,Xiang-Dong Cheng,Jiang-Jiang Qin,Si-Min Qi

doi:10.3389/fphar.2021.692574

Abstract

Proteolysis targeting chimeric (PROTAC) technology is an effective endogenous protein degradation tool developed in recent years that can ubiquitinate the target proteins through the ubiquitin-proteasome system (UPS) to achieve an effect on tumor growth. A number of literature studies on PROTAC technology have proved an insight into the feasibility of PROTAC technology to degrade target proteins. Additionally, the first oral PROTACs (ARV-110 and ARV-471) have shown encouraging results in clinical trials for prostate and breast cancer treatment, which inspires a greater enthusiasm for PROTAC research. Here we focus on the structures and mechanisms of PROTACs and describe several classes of effective PROTAC degraders based on E3 ligases.

Highlights

As a traditional treatment method, chemotherapy plays an irreplaceable role in the cancer treatment process
This paper focuses on introducing the mechanisms and the research progress of Proteolysis targeting chimeric (PROTAC) technology, as well as summarizing the advantages of this degradation method
Different from the traditional small molecule inhibitors (SMIs), PROTAC is a new strategy of inducing the ubiquitination degradation of target proteins

Summary

Introduction

As a traditional treatment method, chemotherapy plays an irreplaceable role in the cancer treatment process. The targeted therapy of cancer has attracted people’s attention (Zhou Y. et al, 2020; Qi et al, 2020; Yu et al, 2020). On this basis, the discoveries of new targets and small molecule inhibitors (SMIs) become powerful treatment strategies (Dong et al, 2018). The development of small molecule kinase inhibitors has become one of the most widely pursued fields in the process of drug discovery and has made great achievements in cancer treatment (Wu et al, 2015). Drug resistance is the main limitation for cancer therapy and needs to be solved urgently

Methods

Findings

Conclusion