Design and Synthesis of Proteolysis Targeting Chimeras for Inducing BRD4 Protein Degradation

Shi-hui, Wang; Li, Haiyan; Wang, Yue; Gao, Yang; Yu, Shanshan; Zhao, Qianqian; Jin, Xiangshu; Lu, Haibin

doi:10.1007/s40242-018-7299-7

Cited by 1 publication

(1 citation statement)

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“…Given the success of PROTACs on different targets, a few factors including the POI binder, linker and E3 ligase, are critical for developing effective degraders. 17,[101][102][103] The selection of the proper POI ligands and E3 ligases is the first and most crucial step. Then, the binding position used for linking the E3 ligase ligands is important in the design, which can be predicted by the binding mode of the POI and its ligand.…”

Section: Introductionmentioning

confidence: 99%

PROTACs: great opportunities for academia and industry

Sun

Gao

Yang

et al. 2019

Sig Transduct Target Ther

438

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Although many kinds of therapies are applied in the clinic, drug-resistance is a major and unavoidable problem. Another disturbing statistic is the limited number of drug targets, which are presently only 20-25% of all protein targets that are currently being studied. Moreover, the focus of current explorations of targets are their enzymatic functions, which ignores the functions from their scaffold moiety. As a promising and appealing technology, PROteolysis TArgeting Chimeras (PROTACs) have attracted great attention both from academia and industry for finding available approaches to solve the above problems. PROTACs regulate protein function by degrading target proteins instead of inhibiting them, providing more sensitivity to drug-resistant targets and a greater chance to affect the nonenzymatic functions. PROTACs have been proven to show better selectivity compared to classic inhibitors. PROTACs can be described as a chemical knockdown approach with rapidity and reversibility, which presents new and different biology compared to other gene editing tools by avoiding misinterpretations that arise from potential genetic compensation and/or spontaneous mutations. PRTOACs have been widely explored throughout the world and have outperformed not only in cancer diseases, but also in immune disorders, viral infections and neurodegenerative diseases. Although PROTACs present a very promising and powerful approach for crossing the hurdles of present drug discovery and tool development in biology, more efforts are needed to gain to get deeper insight into the efficacy and safety of PROTACs in the clinic. More target binders and more E3 ligases applicable for developing PROTACs are waiting for exploration.

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Section: Introductionmentioning

confidence: 99%