机构：[1]Sichuan Cancer Hospital and Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China.四川省人民医院四川省肿瘤医院[2]Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.[3]Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, China.[4]Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Institute for Translational Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, China.
The PROteolysis TArgeting Chimeras (PROTACs) is an innovative technique for the selective degradation of target proteins via the ubiquitin-proteasome system. Compared with traditional protein inhibitor drugs, PROTACs exhibit advantages in the efficacy and selectivity of and in overcoming drug resistance in cancer therapy, providing new insights into the discovery of anti-cancer drugs. In the last two decades, many PROTAC molecules have been developed to induce the degradation of cancer-related targets, and they have been subjected to clinical trials. Here, we comprehensively review the historical milestones and latest updates in PROTAC technology. We focus on the structures and mechanisms of PROTACs and their application in targeting tumor-related targets. We have listed several representative PROTACs based on CRBN, VHL, MDM2, or cIAP1 E3 ligases, and PROTACs that are undergoing anti-cancer clinical trials. In addition, the limitations of the current research, as well as the future research directions are described to improve the PROTAC design and development for cancer therapy.
基金：
This research was supported by the Oncology Medical-Industrial Innovation Fund Project
of University of Electronic Science and Technology, Sichuan Cancer Hospital (Grant No.
ZYGX2021YGCX020), the Sichuan Cancer Hospital Youth Fund Project (Grant No. YB2021035),
the National Natural Science Foundation of China (Grant No. 82204695), the Sichuan Provincial
Research Institutes Basic Research Operations Fund Project (Grant No. A-2022N-Z-2), and the Sichuan
Academy of Traditional Chinese Medicine Research Project (Grant No. QNCJRSC2022-9).
第一作者机构：[1]Sichuan Cancer Hospital and Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Li Rui,Liu Miao,Yang Zhenya,et al.Proteolysis-Targeting Chimeras (PROTACs) in Cancer Therapy: Present and Future[J].MOLECULES.2022,27(24):doi:10.3390/molecules27248828.
APA：
Li Rui,Liu Miao,Yang Zhenya,Li Jiao,Gao Yuxin&Tan Ruirong.(2022).Proteolysis-Targeting Chimeras (PROTACs) in Cancer Therapy: Present and Future.MOLECULES,27,(24)
MLA：
Li Rui,et al."Proteolysis-Targeting Chimeras (PROTACs) in Cancer Therapy: Present and Future".MOLECULES 27..24(2022)
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