Results 61 to 70 of about 7,362 (230)

PROTACs in Oncology: Emerging Frontiers for Next-Generation Cancer Therapeutics

Onco
PROTACs represent a cutting-edge approach to the discovery of innovative cancer therapies. By exploiting the cell’s ubiquitin–proteasome system, PROTACs induce the selective degradation of target proteins, providing a distinct advantage over conventional
Salahuddin, Renu Sharma, Mohamed Jawed Ahsan, Avijit Mazumder, Kavita Rana, Rajnish Kumar, Chandana Majee   +6 more
doaj   +1 more source

Glucose and Glutamine Deprivation Promotes Breast Cancer Lung Metastasis via BRD4‐Dependent Enhancer Activation

Advanced Science, EarlyView.
To model a nutrient‐restricted tumor microenvironment, breast cancer cells were adapted to low glucose and glutamine levels. In the adapted cells, BRD4‐driven enhancer activation increases pro‐invasive EDN1 expression, facilitated by ATF3/c‐JUN and reinforced by enhancer RNA.
Poshan Yugal Bhattarai, Arathy Vasukutty, Yujin Na, Sung‐Chul Lim, Hong Seok Choi   +4 more
wiley   +1 more source

PROTAC-Splitter: A Machine Learning Framework for Automated Identification of PROTAC Substructures

Journal of Cheminformatics
Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules composed of an E3 ligase ligand, a linker, and a warhead targeting a protein of interest. Despite their modular structure, accurately identifying and annotating these components in PROTACs is challenging and typically relies on manual curation and predefined substructure matching.
Ribes, Stefano, Zhang, Ranxuan, Cropsal, Télio, Källberg, Anders, Tyrchan, Christian, Nittinger, Eva, Mercado Oropeza, Rocío   +6 more
openaire   +5 more sources

Near‐Infrared Fluorescent PROTAC Enables Theranostic Imaging and Selective Tau Degradation in Alzheimer's Disease

Advanced Science, EarlyView.
Here, we report a novel NIR fluorescent PROTAC platform that enables real‐time imaging and targeted degradation of Alzheimer's p‐Tau. Our lead compound effectively clears p‐Tau, reduces APP/Aβ, and alleviates cognitive deficits in AD mice. This work demonstrates a theranostic strategy for visualizing degradation and developing next‐generation AD ...
Ziwei Ren, Qian Yue, Ning Gao, Qiu‐Lian Hao, Yan Huo, Chuchu Li, Xinyue Leng, Lu‐Lu Sun, Maggie Pui Man Hoi, Hai‐Hao Han, Mingliang Ma, Xu‐Wen Li   +11 more
wiley   +1 more source

Molecular Glue Degraders Enhance CAPRIN1‐Dependent Lysosomal Degradation of APP and Reduce Amyloid β in Alzheimer's Disease

Advanced Science, EarlyView.
A new class of lysosome‐directed molecular glue degraders selectively enhance CAPRIN1–APP interactions, driving APP degradation and reducing amyloid‐β production in human neurons and Alzheimer's disease mouse models. This CAPRIN1‐dependent targeted protein degradation strategy reveals a previously unrecognized therapeutic approach for disrupting the ...
Sunghan Jung, Xu Wang, Bin Liu, Raktim Roy, Nancy Jaiswal, Ratan K. Rai, Yuichiro Takagi, Cen Gao, Lifan Zeng, Ho‐Yin Lo, Reagan K. Wohlford, Ryan K. Higgins, Bruce T. Lamb, Anantha Shekhar, Anita C. Bellail, Chunhai Hao   +15 more
wiley   +1 more source

Site‐Specific Protein Bioconjugation Through Cellular Incorporation of Noncanonical Amino Acids

Angewandte Chemie, EarlyView.
Genetic code expansion (GCE) enables site‐specific installation of noncanonical amino acids containing bioorthogonal conjugation handles, allowing precise, homogeneous protein modification. This review examines the principles of orthogonal translation, surveys the chemistries available for chemoselective labeling, and highlights emerging multi‐site ...
Rahul Sarkar, Manas Joshi, Abhishek Chatterjee   +2 more
wiley   +2 more sources

Multitargeted protein degradation: Integrating small-molecule, biomacromolecular, and nano-PROTACs for paradigm shifts in drug discovery

Materials Today Advances
Proteolysis-targeting chimeras (PROTACs) have revolutionized drug discovery by enabling targeted protein degradation via the ubiquitin-proteasome system (UPS), overcoming limitations of traditional occupancy-based inhibitors. This innovative approach has
Jinghua Yang, Yujing Zhang, Miao Zhang, Dongming Xing, Chao Wang   +4 more
doaj   +1 more source

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

Advanced Science, EarlyView.
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.
Ke Liu, Xiyan Wang, Xiaozhen Liu, Chaoqi He, Da Qian, Xuli Meng, Liquan Zhu   +6 more
wiley   +1 more source

Generalizable Strategies for the Synthesis of Cereblon-Recruiting PROTAC Prodrugs. [PDF]

Angew Chem Int Ed Engl
Cereblon‐recruiting PROTACs remain challenging to derivatize for prodrug‐based delivery. In this study, three complementary conjugation strategies enabled the efficient synthesis of cleavable PROTAC prodrugs with tunable release kinetics that can be incorporated into a library of PEGylated constructs and bottlebrush prodrugs.
Wang AX, Liu B, Ackerman EM, Xiang Y, Nguyen HV, Jiang Y, Koehler AN, Johnson JA.   +7 more
europepmc   +3 more sources

Chemical Synthesis and Functional Screening of an 800 000‐Member Library Using a Peptide‐Pairing Strategy

Angewandte Chemie, EarlyView.
Chemical peptide synthesis allows the generation of structurally highly diverse compounds suited for ligand development, but current methods in parallel peptide synthesis limit the achievable library size to a few thousand. A strategy is presented based on combinatorial pairing of short peptides via disulfide linkage that enables the generation and ...
Anne Zarda, Xingwang Deng, Edward Will, Thomas Emel, Maylin Romero, Christian Heinis   +5 more
wiley   +2 more sources