Results 101 to 110 of about 504,547 (295)

Artificial intelligence empowers targeted protein degradation: Core technological innovations, multi-scenario applications, and translational prospects. [PDF]

Smart Mol
AI is transforming TPD by improving the design, prediction, and optimization of degraders such as PROTACs, molecular glues, and LYTACs. This review summarizes key AI‐driven advances, highlights applications across drug discovery stages, and discusses remaining challenges and future directions for accelerating the development of therapies against ...
Qin S, Peng R, Zhang G, Yan S, Xiao J, Liu Z, Tan Z, Xie Q, Li S, Luo W, Xiao X.   +10 more
europepmc   +2 more sources

The impact of E3 ligase choice on PROTAC effectiveness in protein kinase degradation.

Drug Discovery Today
Proteolysis targeting chimera (PROTACs) provide a novel therapeutic approach that is revolutionizing drug discovery. The success of PROTACs largely depends on the combination of their three fragments: E3 ligase ligand, linker and protein of interest (POI)
Tomasz Sobierajski, Joanna Małolepsza, Marta Pichlakb, E. Gendaszewska-Darmach, K. Błażewska   +4 more
semanticscholar   +1 more source

In Situ Bioorthogonal Synthesis of PROTACs via Dual‐Responsive Cleavage for Synergistic Photo‐Immunotherapy

Advanced Science, EarlyView.
A bioactive self‐delivering SNAP‐TAC platform responds to tumor‐associated cathepsin B and glutathione, enabling in situ bioorthogonal synthesis of a BRD4‐degrading proteolysis‐targeting chimera within the tumor microenvironment. The resulting BRD4 degradation and PD‐L1 downregulation synergize with photodynamic therapy‐induced immunogenic cell death ...
Shiqin Jian, Jiasha Wu, Fusheng Xu, Yan Zuo, Huaxing Shen, Rui Ji, Luyi Wang, Na Li, Yanting Sun, Yongsheng Yu, Yejiao Shi, Honggang Hu, Feng Xu, Dan Huang, Xiaochun Hu   +14 more
wiley   +1 more source

Rational design of potent small-molecule SMARCA2/A4 degraders acting via the recruitment of FBXO22

Nature Communications
Target-anchored monovalent degraders are more drug-like than their bivalent counterparts, Proteolysis Targeting Chimeras (PROTACs), while offering greater target specificity control than E3 ligase-anchored monovalent degraders, also known as molecular ...
Elisia Villemure, Tom Januario, Mingshuo Zeng, Hanna G. Budayeva, Benjamin T. Walters, Aaron Lictao, Ke Sherry Li, Xiaofen Ye, Caroline L. Gilchrist, Bridget Hoag, Nicholas F. Endres, Peter L. Hsu, John Chan, Tommy K. Cheung, Michael R. Costa, Jean-Philippe Fortin, Noriko Ishisoko, Brett M. Babin, Joyce Liu, Alexandra Frommlet, Joachim Rudolph, Robert L. Yauch   +21 more
doaj   +1 more source

Electrophilic Screening Platforms for Identifying Novel Covalent Ligands for E3 Ligases [PDF]

Biochemistry, 2021
Sijin Zheng, Craig M. Crews
openaire   +2 more sources

Developing Metal–Polyphenol Network‐Based Single‐Protein Particle Encapsulation System for Sustained Release of Whey Protein to Mitigate Sarcopenia

Advanced Science, EarlyView.
Sarcopenia has emerged as a major health challenge in the aging population. Developing a sustained‐release system for whey protein may enhance its effectiveness in mitigating sarcopenia. Herein, a novel “single‐protein particle encapsulation” (SPPE) system is developed to protect whey protein and control its release.
Yafei Zhang, Yuning Zhang, Yongjian Ai, Yao Lu, Heng Quan, Zhen Zhang, Yuqi Wang, Yujia Luo, Xiaoxu Zhang, Yingying Lin, Sijia Song, Huiyuan Guo   +11 more
wiley   +1 more source

Harnessing the SPOP E3 Ubiquitin Ligase via a Bridged Proteolysis Targeting Chimera (PROTAC) Strategy for Targeted Protein Degradation

Journal of Medicinal Chemistry
Proteolysis Targeting Chimeras (PROTACs) represent promising therapeutic modalities for degrading disease-causing proteins. However, the development of effective PROTACs has been limited by the availability of suitable E3 ligase ligands.
Zhi-Jie Deng, Jerrel L. Catlett, Youngeun Lee, Qiong Wu, Zhongli Xu, Ling Xie, Xian Chen, Yan Xiong, H. Kaniskan, Jian Jin   +9 more
semanticscholar   +1 more source

Molecular Signatures of HIV‐Induced Neuroinflammation and Neurodegeneration in Human Cerebral Organoids: Identification of Therapeutic Targets for NeuroHIV

Advanced Science, EarlyView.
HIV preferentially infects microglia, activating IL‐17A‐driven IFN‐γ/STAT1, CEBPB, and NF‐κB signaling that converges with cGAS‐STING and Notch–NEURL1 pathways, promoting neuroinflammation, mitochondrial dysfunction, and synaptic impairment. cART suppresses viral replication, attenuates inflammatory signaling, and at least partially restores ...
Karthick Chennakesavan, Malaroviyam Samikkannu, Shreyan Gupta, Olasunkanmi Israel Tayo, Arpan Acharya, James J. Cai, Siddappa N. Byrareddy, Thangavel Samikkannu   +7 more
wiley   +1 more source

Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity [PDF]

, 2018
Ubiquitination is initiated by transfer of ubiquitin (Ub) from a ubiquitin-activating enzyme (E1) to a ubiquitin-conjugating enzyme (E2), producing a covalently linked intermediate (E2-Ub) 1 . Ubiquitin ligases (E3s) of the 'really interesting new gene' (
Virdee, Satpal; id_orcid, van Aalten, Daan M. F., Peter D. Mabbitt, Pao, Kuan-Chuan, Ramasubramanian Sundaramoorthy, Hofmann, Kay, Rafie, Karim, Wood, Nicola T., Karim Rafie, Satpal Virdee, Mabbitt, Peter D., Knebel, Axel, Daan M. F. van Aalten, Axel Knebel, Stanley, Mathew, Sundaramoorthy, Ramasubramanian, Kay Hofmann, Kuan-Chuan Pao, Nicola T. Wood, Mathew Stanley   +19 more
core   +1 more source

Early‐Life Manganese Overexposure Activates Microglial Phagocytosis through the YY1/TREM2 Axis Leading to Hippocampal Synaptic Remodeling in Mice

Advanced Science, EarlyView.
Early‐life manganese exposure induces behavioral deficits and aberrant hippocampal synaptic remodeling by enhancing microglial phagocytosis in young adult male mice. Mechanistically, manganese promotes Yin Yang 1 (YY1)/triggering receptor expressed on myeloid cells 2 (TREM2) signaling through enhanced HIF1α‐mediated transcription and suppressed SMURF2 ...
Keyu Chen, Bin He, Kuan Liu, Zhuo Ma, Bin Xu   +4 more
wiley   +1 more source