Nano-PROTACs: state of the art and perspectives

Nanoscale, Journal Year: 2024, Volume and Issue: 16(9), P. 4378 - 4391

Published: Jan. 1, 2024

Schematic illustration of the combinational strategy nanotechnology and PROTACs (Nano-PROTACs): typical shortcomings traditional nanotechnology-based strategies for PROTAC drugs optimization.

Language: Английский

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Unveiling the future of metabolic medicine: omics technologies driving personalized solutions for precision treatment of metabolic disorders

Biochemical and Biophysical Research Communications, Journal Year: 2023, Volume and Issue: 682, P. 1 - 20

Published: Sept. 29, 2023

Language: Английский

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PROTACs: A novel strategy for cancer drug discovery and development

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 29, 2023

Proteolysis targeting chimera (PROTAC) technology has become a powerful strategy in drug discovery, especially for undruggable targets/proteins. A typical PROTAC degrader consists of three components: small molecule that binds to target protein, an E3 ligase ligand (consisting and its recruiter), chemical linker hooks first two components together. In the past 20 years, we have witnessed advancement multiple degraders into clinical trials anticancer therapies. However, one major challenges is only very limited number recruiters are currently available as targeted protein degradation (TPD), although human genome encodes more than 600 ligases. Thus, there urgent need identify additional effective TPD applications. this review, summarized existing RING-type ubiquitin their act ligands application discovery. We believe review could serve reference future development efficient cancer discovery development.

Language: Английский

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A programmable targeted protein-degradation platform for versatile applications in mammalian cells and mice

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(8), P. 1585 - 1600.e7

Published: March 12, 2024

Language: Английский

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Cutting-edge biotherapeutics and advanced delivery strategies for the treatment of metabolic dysfunction-associated steatotic liver disease spectrum

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 380, P. 433 - 456

Published: Feb. 11, 2025

Language: Английский

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New strategies to enhance the efficiency and precision of drug discovery

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 11, 2025

Drug discovery plays a crucial role in medicinal chemistry, serving as the cornerstone for developing new treatments to address wide range of diseases. This review emphasizes significance advanced strategies, such Click Chemistry, Targeted Protein Degradation (TPD), DNA-Encoded Libraries (DELs), and Computer-Aided Design (CADD), boosting drug process. Chemistry streamlines synthesis diverse compound libraries, facilitating efficient hit lead optimization. TPD harnesses natural degradation pathways target previously undruggable proteins, while DELs enable high-throughput screening millions compounds. CADD employs computational methods refine candidate selection reduce resource expenditure. To demonstrate utility these methodologies, we highlight exemplary small molecules discovered past decade, along with summary marketed drugs investigational that exemplify their clinical impact. These examples illustrate how techniques directly contribute advancing chemistry from bench bedside. Looking ahead, Artificial Intelligence (AI) technologies interdisciplinary collaboration are poised growing complexity discovery. By fostering deeper understanding transformative this aims inspire innovative research directions further advance field chemistry.

Language: Английский

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Targeted protein degradation in drug development: Recent advances and future challenges

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 261, P. 115839 - 115839

Published: Sept. 27, 2023

Language: Английский

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Breaking Bad Proteins—Discovery Approaches and the Road to Clinic for Degraders

Cells, Journal Year: 2024, Volume and Issue: 13(7), P. 578 - 578

Published: March 26, 2024

Proteolysis-targeting chimeras (PROTACs) describe compounds that bind to and induce degradation of a target by simultaneously binding ubiquitin ligase. More generally referred as bifunctional degraders, PROTACs have led the way in field targeted protein (TPD), with several currently undergoing clinical testing. Alongside single-moiety compounds, or molecular glue degraders (MGDs), are increasingly being considered viable approach for development therapeutics, driven advances rational discovery approaches. This review focuses on drug respect within proteasome system, including analysis mechanistic concepts approaches, an overview current pre-clinical degrader status oncology, neurodegenerative inflammatory disease.

Language: Английский

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Targeted Protein Degradation: Principles and Applications of the Proteasome

Cells, Journal Year: 2023, Volume and Issue: 12(14), P. 1846 - 1846

Published: July 13, 2023

The proteasome is a multi-catalytic protease complex that involved in protein quality control via three proteolytic activities (i.e., caspase-, trypsin-, and chymotrypsin-like activities). Most cellular proteins are selectively degraded by the ubiquitination. Moreover, ubiquitin–proteasome system critical process for maintaining homeostasis. Here, we briefly summarize structure of proteasome, its regulatory mechanisms, regulate activity, alterations to activity found diverse diseases, chemoresistant cells, cancer stem cells. Finally, describe potential therapeutic modalities use system.

Language: Английский

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Potential of the nanoplatform and PROTAC interface to achieve targeted protein degradation through the Ubiquitin–Proteasome system

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 267, P. 116168 - 116168

Published: Feb. 1, 2024

Language: Английский

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