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Current Opinion in Chemical Biology, 2005
The ubiquitin-proteasome pathway plays a major role in cellular protein destruction and regulates fundamental cellular processes such as the cell cycle, cell signaling, and development. By altering the substrate recognition of ubiquitin-protein ligases, their robust proteolytic activity can be re-directed to recruit and accelerate the degradation of ...
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The ubiquitin-proteasome pathway plays a major role in cellular protein destruction and regulates fundamental cellular processes such as the cell cycle, cell signaling, and development. By altering the substrate recognition of ubiquitin-protein ligases, their robust proteolytic activity can be re-directed to recruit and accelerate the degradation of ...
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Leveraging aptamers for targeted protein degradation
Trends in Pharmacological Sciences, 2023Targeted protein degradation (TPD) technologies, particularly proteolysis-targeting chimeras (PROTACs), have emerged as a significant advancement in drug discovery. However, several hurdles - such as the difficulty of identifying suitable ligands for traditionally undruggable proteins, poor solubility and impermeability, nonspecific biodistribution ...
Songbo Xie
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Targeted Protein Degradation via Lysosomes
Biochemistry, 2022In the scope of targeted protein degradation (TPD), proteolysis-targeting chimeras (PROTACs), leveraging the ubiquitin-proteasome system, have been extensively studied. However, they are limited to the degradation of soluble and membrane proteins, excluding the aggregated and extracellular proteins and dysfunctional organelles.
Rishi R. Paudel +4 more
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SnapShot: Targeted protein degradation
CellTargeted protein degradation strategies leverage endogenous cellular degradation machinery to selectively eliminate a protein of interest. Emerging technologies are opening avenues in drug discovery and functional characterization of intracellular, membrane, and extracellular proteins. To view this SnapShot, open or download the PDF.
Yu, Ding, Boxun, Lu
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Development of targeted protein degradation therapeutics
Nature Chemical Biology, 2019Targeted protein degradation as a therapeutic modality has seen dramatic progress and massive investment in recent years because of the convergence of two key scientific breakthroughs: optimization of first-generation peptidic proteolysis-targeted chimeras (PROTACs) into more drug-like molecules able to support in vivo proof of concept and the ...
Philip P, Chamberlain +1 more
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Optical control of targeted protein degradation
Cell Chemical Biology, 2021Molecular glues and proteolysis targeting chimeras (PROTACs) have emerged as small-molecule tools that selectively induce the degradation of a chosen protein and have shown therapeutic promise. Recently, several approaches employing light as an additional stimulus to control induced protein degradation have been reported.
Martin Reynders, Dirk Trauner
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Autophagy‐Mediated Targeted Protein Degradation
ChemMedChemAbstractAutophagy is an evolutionarily conserved turnover process in eukaryotes, mediating the delivery of various cellular components to lysosomes for degradation and facilitating the recycling of the breakdown products to maintain homeostasis.
Jinning Shao +3 more
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Emerging pharmacology of targeted protein degraders
The Journal of Pharmacology and Experimental TherapeuticsTargeted protein degradation is an emerging strategy for experimental and therapeutic ablation of biologically important proteins. To elicit the degradation of their cellular targets, targeted protein degraders act by co-opting the endogenous cellular degradation machineries through chemically-induced proximity.
Samir H. Barghout, Mohamed A. Eldeeb
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Covalent chemistry in targeted protein degradation
Advanced Drug Delivery ReviewsTargeted protein degradation (TPD) has revolutionized drug discovery by enabling the selective removal of specific proteins within and outside cells through the cell's natural degradation pathways. While various TPD modalities have demonstrated immense promise, the integration of covalent chemistry is rapidly emerging as a crucial approach to enhance ...
Jing, Tan +3 more
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Targeted protein degradation for cancer therapy
Nature Reviews CancerTargeted protein degradation (TPD) aims at reprogramming the target specificity of the ubiquitin-proteasome system, the major cellular protein disposal machinery, to induce selective ubiquitination and degradation of therapeutically relevant proteins. Since its conception over 20 years ago, TPD has gained a lot of attention mainly due to improvements ...
Matthias Hinterndorfer +2 more
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