Results 61 to 70 of about 823,777 (226)

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

Kill Two Birds with One Stone: A Multifunctional Dual‐Targeting Protein Drug to Overcome Imatinib Resistance in Philadelphia Chromosome‐Positive Leukemia

Advanced Science, 2022
The Bcr/Abl plays a central role in Philadelphia chromosome‐positive (Ph+) leukemia because of the constitutively activated Abl tyrosine kinase and its downstream pathways.
Bohan Ma, Hui Feng, Chao Feng, Yi Liu, Hailing Zhang, Jincheng Wang, Wenjuan Wang, Pengcheng He, Fan Niu   +8 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

Characteristic roadmap of linker governs the rational design of PROTACs

Acta Pharmaceutica Sinica B
Proteolysis targeting chimera (PROTAC) technology represents a groundbreaking development in drug discovery, leveraging the ubiquitin‒proteasome system to specifically degrade proteins responsible for the disease.
Yawen Dong, Tingting Ma, Ting Xu, Zhangyan Feng, Yonggui Li, Lingling Song, Xiaojun Yao, Charles R. Ashby, Jr, Ge-Fei Hao   +8 more
doaj   +1 more source

Design and characterization of a heterobifunctional degrader of KEAP1

Redox Biology, 2023
The Kelch-like ECH-associated protein 1 (KEAP1) - nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway senses reactive oxygen species and regulates cellular oxidative stress.
Hao Chen, Nghi H. Nguyen, Charlene M. Magtoto, Simon A. Cobbold, Grace M. Bidgood, Lizeth G. Meza Guzman, Lachlan W. Richardson, Jason Corbin, Amanda E. Au, Bernhard C. Lechtenberg, Rebecca Feltham, Kate D. Sutherland, Christoph Grohmann, Sandra E. Nicholson, Brad E. Sleebs   +14 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

De Novo Design of an Androgen Receptor DNA Binding Domain‐Targeted peptide PROTAC for Prostate Cancer Therapy

Advanced Science, 2022
Androgen receptor splice variant‐7 (AR‐V7), one of the major driving factors, is the most attractive drug target in castration‐resistant prostate cancer (CRPC). Currently, no available drugs efficiently target AR‐V7 in clinical practice.
Bohan Ma, Yizeng Fan, Dize Zhang, Yi Wei, Yanlin Jian, Donghua Liu, Zixi Wang, Yang Gao, Jian Ma, Yule Chen, Shan Xu, Lei Li   +11 more
doaj   +1 more source

NAMPT-targeting PROTAC promotes antitumor immunity via suppressing myeloid-derived suppressor cell expansion

Acta Pharmaceutica Sinica B, 2022
Nicotinamide phosphoribosyl transferase (NAMPT) is considered as a promising target for cancer therapy given its critical engagement in cancer metabolism and inflammation.
Ying Wu, Congying Pu, Yixian Fu, Guoqiang Dong, Min Huang, Chunquan Sheng   +5 more
doaj   +1 more source

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

Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer

, 2021
Proteolysis targeting chimera (PROTAC) small-molecule degraders have emerged as a promising new type of therapeutic agents, but the design of PROTAC degraders with excellent oral pharmacokinetics is a major challenge.
Lijie Zhao (721932), Donna McEachern (573068), Chong Qin (2251120), Bo Wen, Weiguo Xiang, Lu Wang (45927), Duxin Sun, Lu Wang, Weiguo Xiang (5536298), Yu Wang, Lijie Zhao, Donna McEachern, Aleksas Matvekas, Aleksas Matvekas (11330597), Bo Wen (207648), Shaomeng Wang, Yu Wang (12152), Shaomeng Wang (88290), Bukeyan Miao (1964026), Hoda Metwally (11330594), Bukeyan Miao, Hoda Metwally, Xin Han, Duxin Sun (501117), Chong Qin, Xin Han (1329648)   +25 more
core   +2 more sources