Results 51 to 60 of about 823,777 (226)

Highly efficient and long-acting split-and-mix proteolysis targeting chimera based on self-assembled polylactic acid

Nature Communications
Proteolysis targeting chimera (PROTAC) technology has received extensive attention due to its “event-driven” mechanism of action. However, existing chimera molecules tend to have higher molecular weight and higher polar surface area and exhibit lower ...
Mei-miao Zhan, Hailing Chen, Meiling He, Chunli Song, Zijun Jiao, Na Liu, Zhihong Liu, Zhanfeng Hou, Ying Chen, Zhibo Song, Yun Xing, Zigang Li, Feng Yin   +12 more
doaj   +1 more source

The ubiquitin system in normal and infected germinal center B cells

FEBS Letters, EarlyView.
The ubiquitin system plays a central role in germinal center (GC) B cells, influencing differentiation to long‐lived memory B cells. Oncogenic gammaherpesviruses gain access to memory B cells by establishing latency in GC B cells. Mapping ubiquitin mechanisms in normal and infected GC B cells will define specific molecular circuits in B cells germane ...
Destiny Davis, Lesly Mejia, Emily K Moser   +2 more
wiley   +1 more source

Selective Protein of Interest Degradation through the Split-and-Mix Liposome Proteolysis Targeting Chimera Approach

, 2023
Proteolysis Targeting Chimera (PROTAC) technology represents a promising new approach for target protein degradation using a cellular ubiquitin-proteasome system.
Qinhong Luo (12535428), Xinrui Sha, Chunli Song (2023402), Yuechen Wang, Zhihong Liu (112690), Yuxin Ye, Zhijun Ruan, Yuhao An, Zhanfeng Hou, Zigang Li, Rui Wang (52434), Zhijun Ruan (12362506), Zigang Li (606370), Yun Xing, Yuechen Wang (6291659), Qinhong Luo, Xinrui Sha (16986747), Chunli Song, Yuxin Ye (9618074), Yun Xing (842497), Zijun Jiao, Zhanfeng Hou (1623067), Fenfang Yang (4584109), Fenfang Yang, Feng Yin, Feng Yin (681489), Rui Wang, Zijun Jiao (16986744), Chenshan Lian, Yuhao An (11197503), Chenshan Lian (8281266), Zhihong Liu   +31 more
core   +1 more source

Inhibition of cyclin‐dependent kinases 12/13 using CT7439 as a treatment for colorectal cancer with CDK12 upregulation

Molecular Oncology, EarlyView.
The proposed mechanism of action for the CDK12/13 inhibitor and cyclin K degrader, CT7439. CDK12/13 inhibition interrupts transcription elongation, leading to increased DNA damage that results in cell death. This agent is a potentially novel treatment option for patients with colorectal cancer. Created in BioRender. Cyclin‐dependent kinase (CDK) 12 and
Wylie K. Watlington, Divya L. Dayanidhi, Mohammad Zokaasadi, John B. Mantyh, Pelumi D. Olawuni, Gabrielle Rupprecht, Jeremy M. Force, Shannon McCall, Ashwani K. Bahl, David S. Hsu, Jason A. Somarelli   +10 more
wiley   +1 more source

Loss of E3 Ubiquitin Ligase RINES via CpG Methylation Relieves Suppression of STAT3 and MYC, Facilitating Multiple Tumorigeneses

Advanced Science, EarlyView.
Dysregulated protein modifications drive tumorigenesis. RINES, an E3 ubiquitin ligase, represses tumor cell proliferation and metastasis by facilitating RING domain‐dependent, ubiquitin–proteasome‐mediated degradation of STAT3 and MYC, which consequently restrains cancer stemness and oncogenic progression.
Lili Li, Ka Man Ng, Xingsheng Shu, Xiaoxue Chai, Kai Yau Wong, Gopesh Srivastava, Anthony T.C. Chan, Wai Yee Chan, Qian Tao   +8 more
wiley   +1 more source

Emerging Strategies in Proteolysis-Targeting Chimeras (PROTACs): Highlights from 2022

International Journal of Molecular Sciences, 2023
Targeted protein degradation (TPD) is a promising therapeutic modality that has garnered attention in academic, industrial, and pharmaceutical research for treating diseases such as cancer, neurodegenerative disorders, inflammation, and viral infections.
Tamatam, Rekha, Shin, Dongyun
openaire   +2 more sources

Targeted Degradation of Picornaviral 3C Protease via PROTACs Confers High Barrier to Viral Resistance and Broad‐Spectrum Antiviral Activity

Advanced Science, EarlyView.
This study reports D34 as the first PROTAC degrader that targets the 3C protease of picornaviruses. D34 effectively degrades EV71 3C protease via the ubiquitin‐proteasome pathway. More importantly, D34 exhibits a high resistance barrier and shows broad‐spectrum antiviral activity against multiple picornaviruses, highlighting its potential as a novel ...
Weilong Deng, Junyu Chen, Yingyue Pang, Yuanyuan Zhang, Siqian Chen, Guoliang You, Xiaoman Tian, Zhongxin Xu, Jing Wang, Luqing Shang   +9 more
wiley   +1 more source

Trafficking Deficiency of TMEM175 Variants in Parkinson's Disease Pathogenesis and the Prospects of Precision Medicine

Advanced Science, EarlyView.
This study identifies that the PD‐associated TMEM175‐L156P variant disrupts lysosomal ion channel trafficking by causing aberrant endoplasmic reticulum retention. A “chaperone–agonist” bifunctional small molecule restores TMEM175‐L156P lysosomal localization and channel function, thereby alleviating PD‐relevant cellular phenotypes and highlighting a ...
Ting Luo, Yu He, Shuyao Li, Haoyu Guan, Ruili Cui, Yu Shi, Zhongwen Jiang, Siyu Wang, Xuan Li, Jiyuan Li, Mei Hu, Yupeng Zhou, Beisha Tang, Yanyan Zhang, Zhaobing Gao, Yu Zhou, Zhenhua Liu, Ping Li   +17 more
wiley   +1 more source

A Single‐Amino‐Acid Ligand for LAT1: A Minimalist and Modular Platform for Lysosome‐Targeted Degradation of Membrane Proteins

Advanced Science, EarlyView.
LA‐LYTAC repurposes the cancer‐enriched amino acid transporter LAT1 as a lysosomal trafficking receptor for targeted membrane‐protein degradation. A single phenylalanine‐derived ligand, modularly linked to antibodies or small‐molecule binders, recruits PD‐L1, EGFR, or integrins to LAT1, triggering transporter‐mediated internalization, lysosomal ...
Liquan Zhu, Ke Liu, Haotian Liu, Chaoqi He, Xiaozhen Liu, Xin Zeng, Misha Mao, Yuxiao Mu, Ying Li, Qinghui Zheng, Hongchao Tang, Da Qian, Xuli Meng   +12 more
wiley   +1 more source

Metabolism-driven in vitro/in vivo disconnect of an oral ERɑ VHL-PROTAC

Communications Biology
Targeting the estrogen receptor alpha (ERα) pathway is validated in the clinic as an effective means to treat ER+ breast cancers. Here we present the development of a VHL-targeting and orally bioavailable proteolysis-targeting chimera (PROTAC) degrader ...
Thomas G. Hayhow, Beth Williamson, Mandy Lawson, Natalie Cureton, Erin L. Braybrooke, Andrew Campbell, Rodrigo J. Carbajo, Azadeh Cheraghchi-Bashi, Elisabetta Chiarparin, Coura R. Diène, Charlene Fallan, David I. Fisher, Frederick W. Goldberg, Lorna Hopcroft, Philip Hopcroft, Anne Jackson, Jason G. Kettle, Teresa Klinowska, Ulrike Künzel, Gillian Lamont, Hilary J. Lewis, Gareth Maglennon, Scott Martin, Pablo Morentin Gutierrez, Christopher J. Morrow, Myria Nikolaou, J. Willem M. Nissink, Patrick O’Shea, Radoslaw Polanski, Markus Schade, James S. Scott, Aaron Smith, Judith Weber, Joanne Wilson, Bin Yang, Claire Crafter   +35 more
doaj   +1 more source