Results 51 to 60 of about 11,335 (243)

Fibrates Inhibit PLTP‐induced M2 Macrophage Infiltration and Increase the Sensitivity of Hepatocellular Carcinoma to ICIs

Advanced Science, EarlyView.
Phospholipid transfer protein(PLTP) plays a critical role in forming a complex with kinase A (AURKA) and P65. This interaction facilitates phosphorylation of P65 at Ser536, leading to the activation of the NF‐κB signaling pathway. Ultimately, this leads to the upregulation of downstream cytokines, including IL‐6, IL‐8, and CSF‐1, which promotes M2 ...
Xinyue Liang, Yaning Li, Jianxun Cai, Lisi Luo, Pengfei Yang, Yutong Chen, Jiancong Zhou, Yan Zeng, Jiaping Yu, Weiyu Zhang, Wenzheng Pang, Yufang Li, Chunhua Wen, Jian Li, Linjuan Zeng   +14 more
wiley   +1 more source

Characteristic roadmap of linker governs the rational design of PROTACs

Acta Pharmaceutica Sinica B
Proteolysis targeting chimera (PROTAC) technology represents a groundbreaking development in drug discovery, leveraging the ubiquitin‒proteasome system to specifically degrade proteins responsible for the disease.
Yawen Dong, Tingting Ma, Ting Xu, Zhangyan Feng, Yonggui Li, Lingling Song, Xiaojun Yao, Charles R. Ashby, Jr, Ge-Fei Hao   +8 more
doaj   +1 more source

Identification of probe-quality degraders for Poly(ADP-ribose) polymerase-1 (PARP-1)

Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Poly(ADP-ribose) polymerase-1 (PARP-1), a critical DNA repair enzyme in the base excision repair pathway, has been pursued as an attractive cancer therapeutic target.
Zhimin Zhang, Xinyue Chang, Chixiao Zhang, Shenxin Zeng, Meihao Liang, Zhen Ma, Zunyuan Wang, Wenhai Huang, Zhengrong Shen   +8 more
doaj   +1 more source

Discovery of SKP2‐Recruiting PROTACs for Target Protein Degradation

Advanced Science, EarlyView.
Based on the SKP2‐targeting ligand SL1, we designed non‐covalent PROTACs by linking it with the BRD4 inhibitor JQ1 and the AR antagonist AL through a linker. These PROTACs successfully induced the ubiquitination of BRD4 and AR, followed by proteasome‐mediated degradation.
Guanjun Dong, Aima Huang, Ziqing Zhao, Bikai Lai, Xin Pan, Huiyu Yang, Xiaohan Xu, Tianwei Wang, Fangchen Zhao, Zhimin Zhang, Yongbo Xue, Guanjun Deng, Wenbin Deng, Jianwei Chen   +13 more
wiley   +1 more source

Interpretable PROTAC Degradation Prediction With Structure‐Informed Deep Ternary Attention Framework

Advanced Science
Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional ligands bridging Proteins‐Of‐Interest (POIs) and E3 ligases for ubiquitin‐proteasome degradation, promising to target the ‘undruggable’.
Zhenglu Chen, Chunbin Gu, Shuoyan Tan, Xiaorui Wang, Yuquan Li, Mutian He, Ruiqiang Lu, Shijia Sun, Chang‐Yu Hsieh, Xiaojun Yao, Huanxiang Liu, Pheng‐Ann Heng   +11 more
doaj   +1 more source

Light-mediated multi-target protein degradation using arylazopyrazole photoswitchable PROTACs (AP-PROTACs)

Chemical Communications, 2022
A new class of arylazopyrazole photoswitchable PROTACs (AP-PROTACs) enables light-triggered degradation of a specific ensemble of protein kinases.
Qisi Zhang, Cyrille S. Kounde, Milon Mondal, Jake L. Greenfield, Jennifer R. Baker, Sergei Kotelnikov, Mikhail Ignatov, Christopher P. Tinworth, Leran Zhang, Daniel Conole, Elena De Vita, Dima Kozakov, Adam McCluskey, John D. Harling, Matthew J. Fuchter, Edward W. Tate   +15 more
openaire   +4 more sources

Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy

Advanced Science, EarlyView.
Lactate, once deemed a metabolic waste, emerges as a central regulator of cancer progression. This review elucidates how lactate and its epigenetic derivative, protein lactylation, orchestrate tumor metabolism, immune suppression, and therapeutic resistance.
Jiajing Gong, Yuhang Xie, Zhijie Weng, Yongzhi Wu, Longjiang Li, Bo Li   +5 more
wiley   +1 more source

Design and development of PROTACs: A new paradigm in anticancer drug discovery

Medicine in Drug Discovery
PROTAC (Proteolysis targeting chimera) is a potential revolutionary strategy in cancer drug development focusing on their ability to target specific receptors like androgen and BRD4, which are vital for the progression and development of several cancers.
Vishal Mathur, Mukund Jha, Iqra Zai, Moksh Mahajan, Shagufi Nazar, Shaheen Ali, Anam Ilyas, Sana Tanweer, Javed Ali, Ozair Alam   +9 more
doaj   +1 more source

Potent and Selective IGF‐IIR‐Recruiting Bifunctional Molecules for Targeted Lysosomal Degradation of Extracellular and Membrane Proteins

Advanced Science, EarlyView.
Lysosome‐targeting chimeras (LYTACs) enable degradation of extracellular and membrane proteins via lysosomal trafficking. We report a novel IGF‐II mutant (Del1–7, Y27L) that selectively engages IGF‐IIR while avoiding IGF‐IR and IR‐A. mutIGF‐II–based LYTACs enhance target internalization and degradation and support a genetically encodable, all‐protein ...
Yuan Zhao, Yaxian Liao, Pengyun Li, Regina Stasser de Gonzalez, Xuankun Chen, Nicholas S. Nieto, Florence M. Brunel, Nick Cox, Joseph Stock, Matthew McHenry, Guangsen Fu, Penghsuan Huang, Wenxin Wu, Deqin Cai, Lingjun Li, Alexander N. Zaykov, Weiping Tang   +16 more
wiley   +1 more source

Challenges in predicting PROTAC-mediated protein–protein interfaces with AlphaFold reveal a general limitation on small interfaces

bioRxiv
Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional molecules composed by ligands binding to a target protein and a E3-ligase complex, connected by a linker, that induce proximity-based target protein degradation.
G. Pereira, Corentin Gouzien, Paulo C. T. Souza, Juliette Martin   +3 more
semanticscholar   +1 more source