Results 51 to 60 of about 7,362 (230)

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

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

In Silico Tools to Extract the Drug Design Information Content of Degradation Data: The Case of PROTACs Targeting the Androgen Receptor

Molecules, 2023
Proteolysis-Targeting Chimeras (PROTACs) have recently emerged as a promising technology in the drug discovery landscape. Large interest in the degradation of the androgen receptor (AR) as a new anti-prostatic cancer strategy has resulted in several ...
Giulia Apprato, Giulia D’Agostini, Paolo Rossetti, Giuseppe Ermondi, Giulia Caron   +4 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

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

Development and Evaluation of Liposomal Celastrol-PROTACs for Treating Triple-Negative Breast Cancer

Pharmaceuticals
Background: Based on our previous study, Celastrol-based proteolysis-targeting chimeras (Celastrol-PROTACs) were shown to induce apoptosis in 4T1 cells by selectively degrading GRP94 and CDK1/4 through the endogenous ubiquitin–proteasome system. However,
Xuebin Li, Chaoqun Yu, Gongyi Zheng, Yanghong Li, Weiguo Cao, Fan Wang   +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

Selective Modulation of OTUB1 Noncanonical Function via a bioPhosTAC Strategy

Advanced Science, EarlyView.
This work positions the versatile performance of the peptide‐based bioPhosTAC platform for dissecting phosphorylation‐dependent biology and expanding the scope of induced‐proximity technologies. We demonstrated that selective manipulation of a tyrosine phosphorylation site is sufficient to propagate coordinated cellular consequences.
Seung Un Seo, Seon Min Woo, Minhyeong Choi, Soeun Rhee, Simmyung Yook, Donghyuk Shin, Kwang‐Su Park, Taeg Kyu Kwon   +7 more
wiley   +1 more source

Artificial intelligence empowers targeted protein degradation: Core technological innovations, multi-scenario applications, and translational prospects. [PDF]

Smart Mol
AI is transforming TPD by improving the design, prediction, and optimization of degraders such as PROTACs, molecular glues, and LYTACs. This review summarizes key AI‐driven advances, highlights applications across drug discovery stages, and discusses remaining challenges and future directions for accelerating the development of therapies against ...
Qin S, Peng R, Zhang G, Yan S, Xiao J, Liu Z, Tan Z, Xie Q, Li S, Luo W, Xiao X.   +10 more
europepmc   +2 more sources

Multi‐Technique Integration Identifies O‐GlcNAc Transferase in Fibroblast‐Like Synoviocytes as a Therapeutic Target for Rheumatoid Arthritis

Advanced Science, EarlyView.
AI‑guided single‑cell transcriptomics identifies OGT as a key regulator enriched in rheumatoid arthritis fibroblast‑like synoviocytes (RA‐FLSs). Inflammatory stimuli activate the OGT–SAP130 axis, which modulates the H3K27ac/H3K27me3 balance and epigenetically silences BTG2, promoting aggressive transformation of RA‑FLSs.
Duoli Xie, Jie Huang, Chunhao Cao, Zhenchao Tang, Xingchen Li, Jianmin Guo, Xinxin Chen, Fang Wang, Dongyi He, Jie Li, Yu Du, Bing He, Jianhua Yao, Aiping Lu, Chao Liang   +14 more
wiley   +1 more source