Results 81 to 90 of about 827,025 (271)

A Small‐Molecule DEPTAC Rescues Cognitive Deficits by Targeted Dephosphorylation of Pathological Tau

Advanced Science, EarlyView.
TP2 is a fully synthetic small‐molecule dephosphorylation‐targeting chimera that recruits endogenous PP2A‐Bα to Tau, enabling targeted removal of pathological phosphate modifications. In two tauopathy mouse models, systemic TP2 reduces Tau pathology, preserves neuronal and synaptic integrity, improves neuroimmune homeostasis, and rescues cognition ...
Fei Sun, Yang Liu, Qiuzhi Zhou, Qingyuan Hu, Weixia Wang, Yue Xiao, Jingfen Su, Guanting Liu, Miaomiao Sun, Lixia Chen, Hua Li, Ying Yang, Jian‐Zhi Wang   +12 more
wiley   +1 more source

Ubiquitous regulation of cerebrovascular diseases by ubiquitin‐modifying enzymes

Clinical and Translational Medicine
Cerebrovascular diseases (CVDs) are a major threat to global health. Elucidation of the molecular mechanisms underlying the pathology of CVDs is critical for the development of efficacious preventative and therapeutic approaches.
Jingyong Huang, Zhenhu Zhu, Dirk Schlüter, Kate Lykke Lambertsen, Weihong Song, Xu Wang   +5 more
doaj   +1 more source

PROTAC‐Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy

Advanced Science, EarlyView.
A PROTAC‐functionalized protein/DNA‐integrated nanoantigen platform is developed to enhance dendritic cell vaccine potency. By combining a VHL‐recruiting peptide‐modified antigen with a sustained expression plasmid within CaCO3 nanoparticles, this system amplifies cross‐presentation, promotes DC maturation, and elicits robust Th1 and CTL responses ...
Peng Liu, Qiang Chen, Zhe Zhou, Yuekang Xu, Jinyao Li   +4 more
wiley   +1 more source

Improving Proteolysis‐Targeting Chimera Delivery by Targeting Key Biomarkers in Tumor Endocytosis Pathways

MedComm – Biomaterials and Applications
Proteolysis‐targeting chimeras (PROTACs) are promising therapeutic agents for targeted protein degradation via the ubiquitin‐proteasome system; however, their clinical application is severely constrained by poor membrane permeability due to high ...
Huahua Chen, Jiayan Jiao, Huiling Yang, Tao He   +3 more
doaj   +1 more source

A New Recruitable E3 Ligase UHRF1 Supporting Targeted Protein Degradation: A Minimal Azide as a Recruitment Ligand

Advanced Science, EarlyView.
Targeted protein degradation is often limited by the scarcity of usable E3 ligases. Herein, we report the first small‐molecule GPX4 degraders that incorporate either electrophilic warheads or a minimal azide group as an E3 recruitment ligand. The azide‐based degrader DK‐5070 effectively drives potent GPX4 degradation; mechanistic studies reveal that ...
Zehong Lin, Kang Duan, Rui Wan, Tao Jiang, Jinzhe Wei, Miao Sun, Mariia A. Skryl'nikova, Maxim A. Gureev, Zhi‐Min Zhang, Zhang Zhang, Ke Ding, Nan Ma, Tongzheng Liu, Yi Tan, Zhengqiu Li   +14 more
wiley   +1 more source

Destruction of DNA‐Binding Proteins by Programmable Oligonucleotide PROTAC (O'PROTAC): Effective Targeting of LEF1 and ERG

Advanced Science, 2021
DNA‐binding proteins, including transcription factors (TFs), play essential roles in various cellular processes and pathogenesis of diseases, deeming to be potential therapeutic targets.
Jingwei Shao, Yuqian Yan, Donglin Ding, Dejie Wang, Yundong He, Yunqian Pan, Wei Yan, Anupreet Kharbanda, Hong‐yu Li, Haojie Huang   +9 more
doaj   +1 more source

Effect of esomeprazole on the pharmacokinetics of vepdegestrant, a PROteolysis TArgeting Chimera oestrogen receptor degrader, in healthy participants. [PDF]

Br J Clin Pharmacol
Aims The aim of this study is to evaluate the effects of multiple doses of esomeprazole, a strong proton pump inhibitor and acid‐reducing agent, on the pharmacokinetics and safety of vepdegestrant, a PROteolysis TArgeting Chimera oestrogen receptor degrader.
Tran L, Chen N, Winton JA, Matschke KT, Goodman SP, Lee KC, Zhang Y, Tan W.   +7 more
europepmc   +2 more sources

A Drug‐Gated, Modular STAb‐T Immunotherapy With External Control

Advanced Science, EarlyView.
Engineered STAb‐TON cells act as programmable living factories that continuously secrete inactive antibody modules, which assemble extracellularly into a functional T cell engager only upon small‐molecule administration. This externally controlled platform enables reversible, on‐demand regulation of antitumor immunity, establishing a new paradigm for ...
Susana Luengo‐Arias, Carmen Domínguez‐Alonso, Ivana Zagorac, Antonio Tapia‐Galisteo, Eva García‐Veros, Laura Rubio‐Pérez, Marina Gómez‐Rosel, Patricia Fuentes, Patricia Hernández‐López, Óscar Aguilar‐Sopeña, Laura Almagro‐Puente, Sonia Martínez‐González, Lucía Cañizares‐Moscato, María Rivas‐Sánchez, Belén Blanco, Ángel Ramírez‐Fernández, Laura Díez‐Alonso, Carmen Blanco‐Aparicio, Javier Arroyo‐Ródenas, Jorge Martínez‐Torrecuadrada, María L. Toribio, Pedro Roda‐Navarro, Anaïs Jiménez‐Reinoso, Luis Álvarez‐Vallina   +23 more
wiley   +1 more source

PTGES3 proteolysis using the liposomal peptide-PROTAC approach

Biology Direct
Background Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide, and the lack of effective biomarkers for early detection leads to poor therapeutic outcomes.
Shiwei Liu, Fukang Yuan, Hui Dong, Jiaqi Zhang, Xinyu Mao, Yangsui Liu, Huansong Li   +6 more
doaj   +1 more source

Supramolecular Degraders: An Emerging Paradigm in Targeted Protein Degradation

Advanced Science, EarlyView.
Dynamic supramolecular assembly reshapes targeted protein degradation by coordinating modular degrader construction, delivery, functional integration, and intracellular assembly or activation across proteasomal, endosomal–lysosomal, and autophagy–lysosomal pathways.
Kongjun Liu, Xue Yuan, Yan Zhou, Rui Yuan, Shaocheng Xie, Yong Chen, Peiyi Wang, Jianmei Gao, Qihai Gong   +8 more
wiley   +1 more source