Results 41 to 50 of about 7,362 (230)

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

pH-Activatable engineered nanoparticle-based selective hexokinase 2 degrader provokes GSDME-dependent pyroptosis for cancer therapy

Acta Pharmaceutica Sinica B
Proteolysis targeting chimeras (PROTACs) technology has been developed as an exquisite promising approach for targeted protein degradation by hijacking the cellular ubiquitin-proteasome system (UPS).
Linlin Gong, Shasha Li, Jiahui Sun, Kunhong Liu, Simeng Wang, Meiju Ji, Peng Hou, Li Yan, Dan Yang, Dechun Liu   +9 more
doaj   +1 more source

Overcoming Cancer Drug Resistance Utilizing PROTAC Technology

Frontiers in Cell and Developmental Biology, 2022
Cancer drug resistance presents a major barrier to continued successful treatment of malignancies. Current therapies inhibiting proteins indicated in cancer progression are consistently found to lose efficacy as a result of acquired drug resistance ...
Matthew R. Burke, Alexis R. Smith, Guangrong Zheng   +2 more
doaj   +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

Computational strategies for PROTAC drug discovery

Acta Materia Medica, 2023
Proteolysis-targeting chimeras (PROTACs), a novel targeted protein degradation technology for potential clinical drug discovery, is composed of a protein-targeting ligand covalently linked to an E3 ligase ligand.
Jia Wu, Wanhe Wang, Chung-Hang Leung
doaj   +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

PROTAC the protein [PDF]

Science-Business eXchange, 2012
GSK and Yale researchers have announced a collaboration to develop a platform that selectively tags disease-associated proteins with an E3 ubiquitin ligase ligand, thus targeting them to a cell's protein degradation machinery. GSK hopes the platform could be a cornerstone for a new Discovery Performance Unit at the pharma and the partners are aiming to
openaire   +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

New-generation advanced PROTACs as potential therapeutic agents in cancer therapy

Molecular Cancer
Proteolysis-targeting chimeras (PROTACs) technology has garnered significant attention over the last 10 years, representing a burgeoning therapeutic approach with the potential to address pathogenic proteins that have historically posed challenges for ...
Chao Wang, Yujing Zhang, Wujun Chen, Yudong Wu, Dongming Xing   +4 more
doaj   +1 more source

Repurposing a Small Molecule Plant Hormone as a Tunable ON‐Switch for CAR‐T Cell Immunotherapy

Advanced Science, EarlyView.
By engineering a receptor system integrating the plant auxin receptor AFB1 with its co‐receptor IAA7, we enable ligand‐dependent interactions triggered by the plant hormone auxins. This design allows rapid, reversible, and dose‐dependent T cell activation, resulting in potent cytotoxicity against B‐cell lymphoma in vitro and in vivo.
Hongxiang Zeng, Lei Zheng, Rongkun Tao, Sirui Zheng, Yanke Zhong, Yongxia Niu, Peng Zhang, Xiang Ma, Chen Yang, Min Zhang, Fuyu Duan, Jing Yang, Xuan Wei, Xiang Zhou, Zhenbiao Yang, Zhaoxi Sun, Qizhou Lian   +16 more
wiley   +1 more source