Results 61 to 70 of about 827,025 (271)

Enhancing Antiproliferative Activity and Selectivity of a FLT‑3 Inhibitor by Proteolysis Targeting Chimera Conversion

, 2018
The receptor tyrosine kinase FLT-3 is frequently mutated in acute myeloid leukemia; however, current small molecule inhibitors suffer from limited efficacy in the clinic. Conversion of a FLT-3 inhibitor (quizartinib) into a proteolysis targeting chimera (
Jayoung Song (758681), Craig M. Crews (135604), John Hines (135601), Xin Chen (14149), George M. Burslem (5987708)   +4 more
core   +2 more sources

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

In vitro and in silico modelling of ROS1‐positive non‐small cell lung cancer reveals fusion‐dependent tyrosine kinase inhibitor responses

Molecular Oncology, EarlyView.
Drug resistance limits treatment success in a subset of lung cancers driven by ROS1 gene alterations. Using patient‐derived cells and computer simulations, we studied three key mutations and how they affect five targeted drugs. The mutations reduced drug effectiveness in different ways by altering protein structure and behavior.
Farhan Ul Haq, Marc Terrones, Felicia Rodrigues Fortes, Anne Schepers, Alessia Denis, Christophe Deben, Ken Op de Beeck, Guy Van Camp, Geert Vandeweyer   +8 more
wiley   +1 more source

From Inhibition to Degradation: Targeting the Anti-apoptotic Protein Myeloid Cell Leukemia 1(MCL1) [PDF]

, 2019
Here we show the development of heterobifunctional small molecules capable of selectively targeting MCL1 using a Proteolysis Targeting Chimera (PROTAC) methodology leading to successful degradation. We have confirmed the involvement of the
Ranjan, Maity, James, Papatzimas, Paola, Neri, Nizar J., Bahlis, Evgueni, Gorobets, Justin L., MacCallum, Darren, Derksen, Mir Ishruna, Muniyat   +7 more
core   +1 more source

Acetylation Targeting Chimera Enables Acetylation of the Tumor Suppressor p53

, 2023
With advances in chemically induced proximity technologies, heterobifunctional modalities such as proteolysis targeting chimeras (PROTACs) have been successfully advanced to clinics for treating cancer.
Tiphaine C. Martin (6577548), Xiaoping Hu (231981), Jingjie Yi, Ramon Parsons (26084), Wei Gu, Tiphaine C. Martin, Jingjie Yi (16450405), Md Kabir (3449078), Yue Zhong, Ning Sun (162468), Yan Xiong (197517), Xiaoping Hu, Jian Jin (351142), Jian Jin, Yan Xiong, H. Ümit Kaniskan, Yue Zhong (1285050), Wei Gu (26249), Ning Sun, Ramon Parsons, H. Ümit Kaniskan (1476325), Md Kabir   +21 more
core   +1 more source

Advances in 3D Bioprinting for Breast Cancer Modeling: Tumor Microenvironment, Metastasis, and Drug Screening

Advanced Healthcare Materials, EarlyView.
Three‐dimensional bioprinting transforms breast cancer modeling from simple constructs into spatially organized, multicellular, perfused, and patient‐derived platforms. This review shows how bioinks, cellular composition, architecture, and flow govern tumor behavior and drug response, while revealing why complexity alone is insufficient without ...
Mustafa Nakipoglu, Mahboobeh Mahmoodi, Ehsanul Hoque Apu, Fahimeh Shahabipour, Sibel Emir Diltemiz, Sanjib Saha, Halima Alem, Nureddin Ashammakhi   +7 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

SOX5 Orchestrates Malignant Evolution via Promoter‐Centric Chromatin Remodeling in MYC‐Driven B‐Cell Lymphoma

Advanced Science, EarlyView.
In MYC‐enforced B‐cell lymphoma, SOX5 occupies promoter‐proximal regulatory regions and is associated with reduced chromatin accessibility at the PCNP locus. PCNP repression promotes proliferative remodeling by limiting apoptosis and cell‐cycle restraint.
Yiyou Mao, Zhenyuan Jia, Xiao‐Qin Mu, Ruilin Wang, Jianli Ma, Qingyuan Zhang, Yuwei Deng   +6 more
wiley   +1 more source

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