Results 101 to 110 of about 14,786 (290)

Leveraging Macrophage Metabolic Reprogramming for Enhanced Anti‐Tumor Immunity

Advanced Science, EarlyView.
Tumor‐associated macrophages (TAMs) are key regulators of the tumor microenvironment (TME), with their metabolic states playing a critical role in tumor progression or regression. This review summarizes current understanding of TAM metabolic plasticity alongside cutting‐edge bioengineering innovations, outlining a roadmap for transforming the ...
Zhiyun Liu, Lingyao Zeng, Xulin Gan, Yilin Zhou, Han Shen, Dan Wu, Xin Shou, Minmin Jiang, Liyun Shi   +8 more
wiley   +1 more source

DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance

Nature Communications
Targeted protein degradation (TPD) is a key modality for drug discovery. Here the authors present the discovery and analysis of reversible DCAF1-PROTACs, which show efficacy in cellular environments resistant to VHL-PROTACs or with acquired resistance to
Martin Schröder, M. Renatus, Xiaoyou Liang, Fabian Meili, Thomas Zoller, S. Ferrand, François Gauter, Xiaoyan Li, Frederic D. Sigoillot, Scott Gleim, Therese-Marie Stachyra, Jason R. Thomas, D. Begue, Maryam Khoshouei, Peggy Lefeuvre, Rita Andraos-Rey, BoYee Chung, Renate Ma, Benika J. Pinch, A. Hofmann, M. Schirle, Niko Schmiedeberg, P. Imbach, Delphine Gorses, Keith Calkins, Beatrice Bauer-Probst, Magdalena Maschlej, Matt Niederst, Robert Maher, Martin Hénault, J. Alford, Erik Ahrné, L. Tordella, Greg Hollingworth, N. Thomä, A. Vulpetti, Thomas Radimerski, Philipp Holzer, Seth Carbonneau, C. Thoma   +39 more
semanticscholar   +1 more source

First Generation Proteolysis Targeting Chimeras (PROTACs) for the Treatment of Progeria

Advanced Science, EarlyView.
We report the first PROTACs designed to degrade progerin, introducing a novel therapeutic approach for progeria. The best compound, UCM‐18142, significantly reduces progerin levels and improves key disease phenotypes in patient‐derived cells and in the LmnaG609G/G609G mouse model, paving the way for new treatment strategies targeting the root cause of ...
Jon Macicior‐Michelena, Marcelino Telechea, Daniel Fernández, Alba García‐Martín, Ángeles Canales, Silvia Ortega‐Gutiérrez   +5 more
wiley   +1 more source

Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex [PDF]

, 2017
Cullin RING E3 ubiquitin ligases (CRLs) function in the ubiquitin proteasome system to catalyze the transfer of ubiquitin from E2 conjugating enzymes to specific substrate proteins.
Adams, Alessio Ciulli, Angers, Babon, Buckley, Buetow, Bulatov, Bulatov, Bullock, Cai, Calabrese, Canning, Cavadini, Chen, Deshaies, Duda, Duda, Duda, Emsley, Evans, Fischer, Fraczkiewicz, Frost, Fulcher, Galdeano, Goldenberg, Hershko, Hon, Jia, Kamura, Kamura, Keegan, Kelsall, Kim, Lai, Lamsoul, Lee, Liu, Liu, Liu, Lu, Lucas, Lydeard, Mahrour, Matthews, Maxwell, McCoy, Min, Morgan S. Gadd, Mosadeghi, Muchnik, Muniz, Nguyen, Nicholls, Onel, Pause, Petroski, Pettersen, Petzold, Prabhu, Salter, Scott, Semenza, Spratt, Stebbins, Teresa A.F. Cardote, Thomas, Vagin, Van Molle, Winn, Winter, Yasgar, Zengerle, Zhao, Zheng   +74 more
core   +2 more sources

ESCRT‐Mimetic Nanodegrader Targets STING for Anti‐Inflammatory Therapy

Advanced Science, EarlyView.
A nanoplatform‐enabled targeted protein degradation strategy is presented to regulate aberrant STING signaling. STING‐ATTEC induces selective autophagic degradation of STING via formation of a STING–ATTEC–LC3 ternary complex, while the cationic FA‐LNP+ system enhances LC3 generation and targeted delivery. Together, this synergistic approach efficiently
Fuyuan Zhou, Qiming Zhai, Zhihao Yao, Qing Li, Yan Yang, Si Wang, Chao Huang, Liangjing Xin, Tao Chen, Jinlin Song   +9 more
wiley   +1 more source

Covalent Reprogramming of Kinase Binders to Modulate Protein Abundance

Advanced Science, EarlyView.
Electrophilic remodeling of a broad‐spectrum kinase binder reveals how subtle chemical changes reprogram protein fate. An acrylamide analog of a multi‐kinase binder selectively stabilizes Aurora kinase A (AURKA) by suppressing its ubiquitination, while a short‐linker variant converts this stabilizer into a degrader.
Chen Mozes, Xiaokang Jin, Miguel A. Campos, Chen Zhou, Xiaoyu Zhang   +4 more
wiley   +1 more source

Ubistatins Inhibit Proteasome-Dependent Degradation by Binding the Ubiquitin Chain [PDF]

, 2004
To identify previously unknown small molecules that inhibit cell cycle machinery, we performed a chemical genetic screen in Xenopus extracts. One class of inhibitors, termed ubistatins, blocked cell cycle progression by inhibiting cyclin B proteolysis ...
Coffino, Philip, D'Onofrio, Mariapina, Deshaies, Raymond J., Fushman, David, King, Randall W., Peters, Noel R., Sakamoto, Kathleen M., Tochtrop, Gregory P., Varadan, Ranjani, Verma, Rati, Zhang, Mingsheng   +10 more
core   +2 more sources

Rational Design of Broad‐Spectrum Anti‐Enteroviral Molecular Glues Targeting Enteroviral RNAi Suppressors

Advanced Science, EarlyView.
By leveraging this homodimerization mechanism, molecular glues were rationally designed to induce dysfunctional 3A dimerization, thereby restoring antiviral RNAi. The optimal molecular glue, VTP‐32, demonstrated potent and pan‐enterovirus (groups A, B, D) antiviral effects.
Yuan Fang, Xiong Xie, Huidi Fan, Botao Wu, An Wang, Wenhao Dai, Zezhong Liu, Jian Li, Huoyan Tong, Jianan Li, Yujie Ren, Jinlin Wang, Xi Zhou, Hong Liu   +13 more
wiley   +1 more source

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

Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs

EBioMedicine, 2018
There are several challenges towards the development and clinical use of small molecule inhibitors, which are currently the main type of targeted therapies towards intracellular proteins. PROteolysis-TArgeting Chimeras (PROTACs) exploit the intracellular
Sainan An, Liwu Fu
doaj   +1 more source