Journal ArticleDOI
Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy.
Liguo Wang,Xuejing Shao,Tianbai Zhong,Yue Wu,Aixiao Xu,Xiuyun Sun,Hongying Gao,Yongbo Liu,Tianlong Lan,Yan Tong,Xue Tao,Wenxin Du,Wei Wang,Yingqian Chen,Ting Li,Xianbin Meng,Haiteng Deng,Bo Yang,Qiaojun He,Meidan Ying,Yu Rao,Yu Rao +21 more
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TLDR
Wang et al. as mentioned in this paper developed first-in-class CDK2-targeted proteolysis-targeting chimeras (PROTACs), which promoted rapid and potent CDK 2 degradation in different cell lines without comparable degradation of other targets.Abstract:
The discovery of effective therapeutic treatments for cancer via cell differentiation instead of antiproliferation remains a great challenge. Cyclin-dependent kinase 2 (CDK2) inactivation, which overcomes the differentiation arrest of acute myeloid leukemia (AML) cells, may be a promising method for AML treatment. However, there is no available selective CDK2 inhibitor. More importantly, the inhibition of only the enzymatic function of CDK2 would be insufficient to promote notable AML differentiation. To further validate the role and druggability of CDK2 involved in AML differentiation, a suitable chemical tool is needed. Therefore, we developed first-in-class CDK2-targeted proteolysis-targeting chimeras (PROTACs), which promoted rapid and potent CDK2 degradation in different cell lines without comparable degradation of other targets, and induced remarkable differentiation of AML cell lines and primary patient cells. These data clearly demonstrated the practicality and importance of PROTACs as alternative tools for verifying CDK2 protein functions.read more
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Journal ArticleDOI
RNA m6A demethylase FTO-mediated epigenetic up-regulation of LINC00022 promotes tumorigenesis in esophageal squamous cell carcinoma
Yuanbo Cui,Chunyan Zhang,Shanshan Ma,Zhe Li,Wenjie Wang,Ya Li,Yingchao Ma,Jiarui Fang,Yaping Wang,Wei Cao,Fangxia Guan +10 more
TL;DR: In this paper, the effects of epigenetic modification of LncRNA on esophageal squamous cell carcinoma (ESCC) were investigated in vitro and in vivo.
Journal ArticleDOI
Developments of CRBN-based PROTACs as potential therapeutic agents
TL;DR: A comprehensive review on the latest research progress in CRBN-based PROTACs can be found in this paper, where the degradants are presented in alphabetical order by target.
Journal ArticleDOI
PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)
TL;DR: Proteolysis TArgeting Chimeras (PROTACs) technology is a new protein-degradation strategy that has emerged in recent years as discussed by the authors , which uses bifunctional small molecules to induce the ubiquitination and degradation of target proteins through a ubiquitin-proteasome system.
Journal ArticleDOI
Chemistries of bifunctional PROTAC degraders.
TL;DR: This review highlights the important advances in this rapidly growing field and critical limitations of the traditional trial-and-error approach to developing PROTACs by analyzing numerous representative examples of Protolysis targeting chimeras development.
Journal ArticleDOI
Target and tissue selectivity of PROTAC degraders.
TL;DR: Critical analysis of the recent progress towards making selective PROTAC molecules and new PROTAC technologies that will continue to push the boundaries of achieving selectivity are provided.
References
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Journal ArticleDOI
Structural basis of PROTAC cooperative recognition for selective protein degradation.
M.S. Gadd,Andrea Testa,Xavier Lucas,Kwok-Ho Chan,Wenzhang Chen,Douglas J. Lamont,Michael Zengerle,Alessio Ciulli +7 more
TL;DR: The results elucidate how PROTAC-induced de novo contacts dictate preferential recruitment of a target protein into a stable and cooperative complex with an E3 ligase for selective degradation.
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