Leveraging aptamers for targeted protein degradation

Yang, Zhihao; Pang, Qiuxiang; Zhou, Jun; Xuan, Chenghao; Xie, Songbo

doi:10.1016/j.tips.2023.05.008

Cited by 17 publications

(1 citation statement)

References 79 publications

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“…However, issues such as poor cell membrane permeability and instability have hindered their broader clinical application. These PROTACs were polar, leading to poor permeability, a problem that persists even in modern designs (Ma, Fan, et al, 2022; Yang, Pang, et al, 2023).…”

Section: The Types Of Classic Protacsmentioning

confidence: 99%

Restraining the power of Proteolysis Targeting Chimeras in the cage: A necessary and important refinement for therapeutic safety

Zhang,

Xie,

Ran

et al. 2024

Journal Cellular Physiology

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Proteolysis Targeting Chimeras (PROTACs) represent a significant advancement in therapeutic drug development by leveraging the ubiquitin‐proteasome system to enable targeted protein degradation, particularly impacting oncology. This review delves into the various types of PROTACs, such as peptide‐based, nucleic acid‐based, and small molecule PROTACs, each addressing distinct challenges in protein degradation. It also discusses innovative strategies like bridged PROTACs and conditional switch‐activated PROTACs, offering precise targeting of previously “undruggable” proteins. The potential of PROTACs extends beyond oncology, with ongoing research and technological advancements needed to maximize their therapeutic potential. Future progress in this field relies on interdisciplinary collaboration and the integration of advanced computational tools to open new treatment avenues across various diseases.

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Section: The Types Of Classic Protacsmentioning

confidence: 99%

Restraining the power of Proteolysis Targeting Chimeras in the cage: A necessary and important refinement for therapeutic safety

Zhang,

Xie,

Ran

et al. 2024

Journal Cellular Physiology

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High‐Throughput Miniaturized Synthesis of PROTAC‐Like Molecules

Tian,

Seifermann,

Bauer

et al. 2024

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The development of miniaturized high‐throughput in situ screening platforms capable of handling the entire process of drug synthesis to final screening is essential for advancing drug discovery in the future. In this study, an approach based on combinatorial solid‐phase synthesis, enabling the efficient synthesis of libraries of proteolysis targeting chimeras (PROTACs) in an array format is presented. This on‐chip platform allows direct biological screening without the need for transfer steps. UV‐induced release of target molecules into individual droplets facilitates further on‐chip experimentation. Utilizing a mitogen‐activated protein kinase kinases (MEK1/2) degrader as a template, a series of 132 novel PROTAC‐like molecules is synthesized using solid‐phase Ugi reaction. These compounds are further characterized using various methods, including matrix‐assisted laser desorption ionization mass spectrometry (MALDI‐MS) imaging, while consuming only a few milligrams of starting materials in total. Furthermore, the feasibility of culturing cancer cells on the modified spots and quantifying the effect of MEK suppression is demonstrated. The miniaturized synthesis platform lays a foundation for high‐throughput in situ biological screening of potent PROTACs for potential anticancer activity and offers the potential for accelerating the drug discovery process by integrating miniaturized synthesis and biological steps on the same array.

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