Emerging protein degradation strategies: expanding the scope to extracellular and membrane proteins.
Jiayi Lin,Jinmei Jin,Yi-Wen Shen,Li-Jun Zhang,Gang Gong,Huiting Bian,Hong-Zhuan Chen,Dale G. Nagle,Ye Wu,Weidong Zhang,Weidong Zhang,Xin Luan +11 more
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Abstract:
Classic small molecule inhibitors that directly target pathogenic proteins typically rely on the accessible binding sites to achieve prolonged occupancy and influence protein functions. The emerging targeted protein degradation (TPD) strategies exemplified by PROteolysis TArgeting Chimeras (PROTACs) are revolutionizing conventional drug discovery modality to target proteins of interest (POIs) that were categorized as "undruggable" before, however, these strategies are limited within intracellular POIs. The novel new degrader technologies such as LYsosome-TArgeting Chimaeras (LYTACs) and Antibody-based PROTACs (AbTACs) have been successfully developed to expand the scope of TPD to extracellular and membrane proteins, fulfilling huge unmet medical needs. Here, we systematically review the currently viable protein degradation strategies, emphasize that LYTACs and AbTACs turn a new avenue for the development of TPD, and highlight the potential challenges and directions in this vibrant field.read more
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Targeted protein degradation: mechanisms, strategies and application
TL;DR: In this article , the authors summarize recent advances of major targeted protein degradation (TPD) technologies, discuss their potential applications, and hope to provide a prime for both biologists and chemists who are interested in this vibrant field.
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Molecular Glues: The Adhesive Connecting Targeted Protein Degradation to the Clinic
TL;DR: This paper uses data from the CAS Content Collection and the publication landscape of recent research on targeted protein degraders to provide insights into these molecules, with a special focus on molecular glues.
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Small-Molecule PROTACs for Cancer Immunotherapy
TL;DR: This review attempts to comprehensively summarize the well-studied and less-developed immunological targets available for PROTAC technology, as well as some targets to be explored, aiming to provide more options and opportunities for the development of small-molecule-based tumor immunotherapy.
Journal ArticleDOI
Non-small molecule PROTACs (NSM-PROTACs): Protein degradation kaleidoscope
Sinan Ma,Jian-Ai Ji,Yuanyuan Tong,Yuxuan Zhu,Junwei Dou,Xian Zhang,Shicheng Xu,Tianbao Zhu,Xiao-Li Xu,Qidong You,Zheng-Yu Jiang +10 more
TL;DR: In this article , the authors introduce the types of non-small molecule PROTACs, describe the advantages of NSM-PROTACs and summarize the development of NMT-PROPACs so far in detail.
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Carnosol alleviates nonalcoholic fatty liver disease by inhibiting mitochondrial dysfunction and apoptosis through targeting of PRDX3.
Yunfei Geng,Yue Wang,Ruimin Sun,Xiaohui Kang,Huanyu Zhao,Meiyang Zhu,Yu Sun,Yan Hu,Zhecheng Wang,Xiaofeng Tian,Yan Zhao,Jihong Yao +11 more
TL;DR: Wang et al. as mentioned in this paper investigated the protective effect of the natural phenolic compound CAR on NAFLD via Peroxiredoxin 3 (PRDX3), a mitochondrial H2O2-eliminating enzyme, undergoes overoxidation and subsequent inactivation under oxidative stress.
References
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Smac Mimetics Activate the E3 Ligase Activity of cIAP1 Protein by Promoting RING Domain Dimerization
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