Histone Deacetylases as Epigenetic Targets for Treating Parkinson’s Disease DOI Creative Commons

Yan Li,

Zhicheng Gu, Shuxian Lin

et al.

Brain Sciences, Journal Year: 2022, Volume and Issue: 12(5), P. 672 - 672

Published: May 21, 2022

Parkinson’s disease (PD) is a chronic progressive neurodegenerative that increasingly becoming global threat to the health and life of elderly worldwide. Although there are some drugs clinically available for treating PD, these treatments can only alleviate symptoms PD patients but cannot completely cure disease. Therefore, exploring other potential mechanisms develop more effective modify course still highly desirable. Over last two decades, histone deacetylases, as an important group epigenetic targets, have attracted much attention in drug discovery. This review focused on current knowledge about deacetylases involved pathophysiology their inhibitors used studies. Further perspectives related small molecules inhibit or degrade treat were also discussed.

Language: Английский

Molecular hybridization: a powerful tool for multitarget drug discovery DOI
Pedro de Sena Murteira Pinheiro, Lucas Silva Franco, Tadeu L. Montagnoli

et al.

Expert Opinion on Drug Discovery, Journal Year: 2024, Volume and Issue: 19(4), P. 451 - 470

Published: March 8, 2024

Introduction The current drug discovery paradigm of 'one drug, multiple targets' has gained attention from both the academic medicinal chemistry community and pharmaceutical industry. This is in response to urgent need for effective agents treat multifactorial chronic diseases. molecular hybridization strategy a useful tool that been widely explored, particularly last two decades, design multi-target drugs.

Language: Английский

Citations

44
Nano-PROTACs: state of the art and perspectives DOI
Jie Zhong, Ruiqi Zhao, Yuji Wang

et al.

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

Citations

19
Transitioning from wet lab to artificial intelligence: a systematic review of AI predictors in CRISPR DOI Creative Commons

Ahtisham Fazeel Abbasi,

Muhammad Nabeel Asim,

Andreas Dengel

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 4, 2025

Abstract The revolutionary CRISPR-Cas9 system leverages a programmable guide RNA (gRNA) and Cas9 proteins to precisely cleave problematic regions within DNA sequences. This groundbreaking technology holds immense potential for the development of targeted therapies wide range diseases, including cancers, genetic disorders, hereditary diseases. based genome editing is multi-step process such as designing precise gRNA, selecting appropriate Cas protein, thoroughly evaluating both on-target off-target activity Cas9-gRNA complex. To ensure accuracy effectiveness system, after cleavage, requires careful analysis resultant outcomes indels deletions. Following success artificial intelligence (AI) in various fields, researchers are now leveraging AI algorithms catalyze optimize system. achieve this goal AI-driven applications being integrated into each step, but existing predictors have limited performance many steps still rely on expensive time-consuming wet-lab experiments. primary reason behind low gap between CRISPR fields. Effective integration demands comprehensive knowledge domains. paper bridges research. It offers unique platform grasp deep understanding biological foundations step process. Furthermore, it provides details 80 available system-related datasets that can be utilized develop applications. Within landscape process, insights representation learning methods, machine methods trends, values 50 predictive pipelines. In context classifiers/regressors, thorough pipelines recommendations more robust

Language: Английский

Citations

2
Research in the Field of Drug Design and Development DOI Creative Commons
Grażyna Biała, Ewa Kędzierska, Marta Kruk-Słomka

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(9), P. 1283 - 1283

Published: Sept. 11, 2023

The processes used by academic and industrial scientists to discover new drugs have recently experienced a true renaissance, with many exciting techniques being developed over the past 5-10 years alone. Drug design discovery, search for safe well-tolerated compounds, as well ineffectiveness of existing therapies, society's insufficient knowledge concerning prophylactics pharmacotherapy most common diseases today, comprise serious challenge. This can influence not only quality human life, but also health whole societies, which became evident during COVID-19 pandemic. In general, process drug development consists three main stages: preclinical using cell-based animal models/tests, clinical trials on humans and, finally, forward moving toward step obtaining regulatory approval, in order market potential drug. this review, we will attempt outline first important consecutive phases development, based experience cooperating complementary centers Visegrád group; i.e., Medical University Lublin, Poland, Masaryk Brno, Czech Republic, Comenius Bratislava, Slovak Republic.

Language: Английский

Citations

27
Application of Novel Degraders Employing Autophagy for Expediting Medicinal Research DOI
Xiang Li, Qian Liu, Xin Xie

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(3), P. 1700 - 1711

Published: Jan. 30, 2023

Targeted protein degradation (TPD) technology is based on a unique pharmacological mechanism that has profoundly revolutionized medicinal research by overcoming limitations associated with traditional small-molecule drugs. Autophagy, for intracellular waste disposal and recovery, an important biological process in research. Recently, studies have demonstrated several emerging autophagic degraders can treat human diseases. Herein we summarize the progress degraders, including autophagosome-tethering compounds (ATTEC), autophagy-targeting chimeras (AUTAC), AUTOphagy-TArgeting (AUTOTAC), treating These exhibit excellent potential neurodegenerative Our provides new avenue TPD via autophagy.

Language: Английский

Citations

25
Sequential responsive nano-PROTACs for precise intracellular delivery and enhanced degradation efficacy in colorectal cancer therapy DOI Creative Commons
Liuqing Yang, Ye Yang, Jing Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 18, 2024

PROteolysis TArgeting Chimeras (PROTACs) have been considered the next blockbuster therapies. However, due to their inherent limitations, efficacy of PROTACs is frequently impaired by limited tissue penetration and particularly insufficient cellular internalization into action sites. Herein, based on ultra-pH-sensitive enzyme-sensitive nanotechnology, a type polymer PROTAC conjugated pH/cathepsin B sequential responsive nanoparticles (PSRNs) are deliberately designed, following construction for Cyclin-dependent kinase 4 6 (CDK4/6). Colorectal cancer (CRC) which hardly responds many treatments even immune checkpoint blockades was selected as tumor model in this study. As result, PSRNs were found maintain nanostructure (40 nm) circulation efficiently accumulated tumors via enhanced permeation retention effect. Then, they dissociated unimers (<10 response an acidic microenvironment, facilitating internalization. Eventually, CDK4/6 degrading released intracellularly cleavage cathepsin B. Importantly, led degradation target protein vitro vivo. The also augmented blockades, through upregulation programmed cell death-ligand 1 (PD-L1) expression cells suppression regulatory T proliferation microenvironment. By combination with α-PD-1, anti-tumor outcome well achieved CT26 model. Overall, our study verifies significance precise intracellular delivery introduces promising therapeutic strategy targeted treatment CRC.

Language: Английский

Citations

11
PROTAC-biomacromolecule conjugates for precise protein degradation in cancer therapy: A review DOI
Chao Wang, Yujing Zhang, Wanpeng Yu

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 261, P. 129864 - 129864

Published: Jan. 30, 2024

Language: Английский

Citations

10
MEGA PROTAC, MEGA DOCK-based PROTAC mediated ternary complex formation pipeline with sequential filtering and rank aggregation DOI Creative Commons

Sadettin Yavuz Ugurlu,

David W. McDonald,

Ramazan Enisoglu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 14, 2025

Language: Английский

Citations

1
In silico modeling of targeted protein degradation DOI Creative Commons
Wenxing Lv,

Xiaojuan Jia,

Bowen Tang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 289, P. 117432 - 117432

Published: Feb. 20, 2025

Language: Английский

Citations

1
Advancing targeted protein degradation for metabolic diseases therapy DOI Creative Commons
Qianqian Zhou, Haitao Xiao, Fan Yang

et al.

Pharmacological Research, Journal Year: 2022, Volume and Issue: 188, P. 106627 - 106627

Published: Dec. 21, 2022

The development and application of traditional drugs represented by small molecule chemical biological agents, especially inhibitors, have become the mainstream drug development. In recent years, targeted protein degradation (TPD) technology has one most promising methods to remove specific disease-related proteins using cell self-destruction mechanisms. Many different TPD strategies are emerging based on ubiquitin-proteasome system (UPS) autophagy-lysosomal pathway (ALP), including but not limited proteolysis-targeting chimeras (PROTAC), molecular glues (MG), lysosome targeting (LYTAC), chaperone-mediated autophagy (CMA)-targeting chimeras, autophagy-targeting chimera (AUTAC), autophagosome-tethering compound (ATTEC), (AUTOTAC). advent can change targets in human cells from undruggable druggable, greatly expanding therapeutic prospect refractory diseases such as metabolic syndrome. Here, we summarize latest progress major technologies, syndrome look forward providing new insights for discovery.

Language: Английский

Citations

34