Results 1 to 10 of about 1,524 (124)

Targeted protein degradation dismantles undruggable targets to reverse immune evasion and therapy resistance in cancer [PDF]

Frontiers in Immunology
Targeted protein degradation (TPD) harnesses endogenous proteolytic machineries—the ubiquitin–proteasome system and lysosomal pathways—to selectively eliminate disease-causing proteins that are refractory to conventional inhibition.
Furong Zhang, Furong Zhang, Qianheng Wang, Qianheng Wang, Mingxuan Li, Tingting Wang, Ping Lei, Tao Huang, Zhenghao Wu, Zhenghao Wu, Zhenghao Wu   +10 more
doaj   +2 more sources

Supramolecular Degraders: An Emerging Paradigm in Targeted Protein Degradation. [PDF]

Adv Sci (Weinh)
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.
Liu K, Yuan X, Zhou Y, Yuan R, Xie S, Chen Y, Wang P, Gao J, Gong Q.   +8 more
europepmc   +2 more sources

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

Targeted Lysosomal Degradation of Extracellular and Membrane Proteins: From Receptor Hijacking to Programmable Endolysosomal Routing. [PDF]

Adv Sci (Weinh)
Targeted chimeric degraders engage extracellular or membrane proteins and endocytosable cell‐surface receptors, forming ternary complexes that induce receptor‐mediated internalization. Following endocytosis, post‐endocytic sorting—not internalization alone—determines target fate.
Liu K, Wang X, Liu X, He C, Qian D, Meng X, Zhu L.   +6 more
europepmc   +2 more sources

Targeted proteoform degradation for precision drug design, delivery, and therapy [PDF]

Drug Delivery
Ubiquitin-proteasome system (UPS)-mediated targeted protein degradation (TPD) is a central mechanism of maintaining protein homeostasis, which is closely associated with multiple diseases.
Chenyu Cui, Haoyue Zhang, Xinmiao Wang, Na Li, Xianquan Zhan   +4 more
doaj   +2 more sources

A quantitative approach for defining the degradability landscape of protein degraders [PDF]

Nature Communications
Targeted protein degradation (TPD) is an emerging therapeutic modality, but how multiple factors jointly determine degradation efficacy remains poorly understood.
Wei Du, Lamberto De Boni, Benjamin David Hopkins, Olivier Elemento   +3 more
doaj   +2 more sources

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

Adv Sci (Weinh)
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 ...
Lin Z, Duan K, Wan R, Jiang T, Wei J, Sun M, Skryl'nikova MA, Gureev MA, Zhang ZM, Zhang Z, Ding K, Ma N, Liu T, Tan Y, Li Z.   +14 more
europepmc   +2 more sources

From PROTAC to TPD: Advances and Opportunities in Targeted Protein Degradation

Pharmaceuticals
PROTAC is a rapidly developing engineering technology for targeted protein degradation using the ubiquitin–proteasome system, which has promising applications for inflammatory diseases, neurodegenerative diseases, and malignant tumors. This paper gives a
Siqi Wang, Fuchu He, Chunyan Tian, Aihua Sun   +3 more
doaj   +3 more sources

Hydrophobic Tag Protein Degraders: An Emerging Therapeutic Strategy for Cancer [PDF]

Pharmaceuticals
Hydrophobic tag degraders (HyTDs) are a promising strategy for achieving targeted protein degradation (TPD). HyTDs are composed of a hydrophobic moiety conjugated via a linker to a ligand that binds to the protein of interest (POI).
Tania Aguilera-Pineda, Siddhartha Kumar, Gargi Ghosal, Amarnath Natarajan, Adam R. Karpf   +4 more
doaj   +2 more sources

Mapping Scientific Landscapes and Therapeutic Innovations of Targeted Protein Degradation: A Scientometric Review [PDF]

Pharmaceutics
Targeted Protein Degradation (TPD) has emerged as a transformative paradigm in drug discovery, offering a robust strategy to address “undruggable” targets.
Chong Li, Xiangxiu Wang, Anqi He, Tianjie Bao, Weihua Zhuang, Chengqi He, Yonghong Yang   +6 more
doaj   +2 more sources