Results 61 to 70 of about 8,212 (230)

Proteasomal and lysosomal degradation for specific and durable suppression of immunotherapeutic targets

Cancer Biology & Medicine, 2020
Cancer immunotherapy harness the body’s immune system to eliminate cancer, by using a broad panel of soluble and membrane proteins as therapeutic targets.
Yungang Wang, Shouyan Deng, Jie Xu
doaj   +1 more source

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

Targeting IRAK4 for Degradation with PROTACs [PDF]

ACS Medicinal Chemistry Letters, 2019
Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) is a key mediator of innate immunity. IRAK4 overactivation is linked with several autoimmune diseases. To date, many IRAK4 inhibitors have been developed to block the protein's kinase activity with the most advanced reaching Phase II clinical trials.
Joao Nunes, Grant A. McGonagle, Jessica Eden, Girieshanie Kiritharan, Megane Touzet, Xiao Lewell, John Emery, Hilary Eidam, John D. Harling, Niall A. Anderson   +9 more
openaire   +2 more sources

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

Orthogonal Light- and Enzyme-Triggered and-Gate Prodrugs for Senolytic Therapy. [PDF]

Adv Sci (Weinh)
An orthogonal AND‐gate prodrug platform combines 390 nm near‐UV photocleavage with SA‐β‐gal activation to control payload release in senescent cells. Its modular architecture enables 4‐MU fluorescence, doxorubicin‐mediated cytotoxicity, and ARV‐771‐driven BRD4 degradation, supporting stimulus‐controlled senolytic design in cellular and organoid models.
Chang M, Zhang K, Wang J, Bi F, Dai Z, Yang M, Liu M, Peng H, Zhang F, Guo Y, Dai J, Liu Q, Wang W.   +12 more
europepmc   +2 more sources

Advantages of PROTACs in achieving selective degradation of homologous protein families

Beilstein Journal of Organic Chemistry
Proteolysis-targeting chimeras (PROTACs) have emerged as a promising therapeutic modality and now represent an important addition to the toolkit of medicinal chemists.
Luxi Yang, Xinfei Mao, Jingyi Zhang, Jing Shu, Wenhai Huang, Xiaowu Dong, Yinqiao Chen, Mingfei Wu   +7 more
doaj   +1 more source

VHL-recruiting PROTAC attenuates renal fibrosis and preserves renal function via simultaneous degradation of Smad3 and stabilization of HIF-2α

Cell & Bioscience, 2022
Background Renal fibrosis is the pathological foundation of various chronic kidney diseases progressing to end stage renal failure. However, there are currently no nephroprotective drugs targeted to the fibrotic process in clinical practice.
Jiayi Yang, Yuyi Ruan, Dan Wang, Jinjin Fan, Ning Luo, Huiting Chen, Xiaoyan Li, Wei Chen, Xin Wang   +8 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

Proteolysis-targeting chimera (PROTAC) in cancer: design principles and applications on "undruggable" targets. [PDF]

Biomark Res
Targeted cancer therapies can enhance in vivo efficacy and decrease side effects by changing the distribution and exposure of specific biomolecules in tissues.
Lu X, Qin J, Dong S, Yuan Y, Zhang Z, Zhang B, Chen X, Gan X, Liang H, Liu F.   +9 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