Results 81 to 90 of about 1,821,409 (281)

Deep Contrastive Learning for High‐Throughput Prediction of Drug Resistance Mutations from Sequences

Advanced Science, EarlyView.
This study presents DeepMutDTA, a deep learning framework aimed at predicting mutation‐induced changes in protein‐drug interactions and prioritizing variants potentially linked to drug resistance. Trained on large‐scale data, it incorporates SimSiam‐MuTF, a label‐aware contrastive fine‐tuning strategy that encourages separation between WT and MT ...
Xiaowen Hu, Pan Zhang, Shangqian Wu, Hao Sun, Minwei Li, Sophia Tsoka, Zizhang Sheng, Lei Deng   +7 more
wiley   +1 more source

Drug Repositioning: Current Advances and Future Perspectives

, 2019
Drug repositioning is the process of identifying new indications for existing drugs. At present, the conventional de novo drug discovery process requires an average of about 14 years and US$2.5 billion to approve and launch a drug. Drug repositioning can
Yuhei Nishimura, Hideaki Hara
core   +1 more source

Lactate‐Driven Restriction of Mitochondrial Permeability Transition Promotes Resistance to Chemo‐Immunotherapy by Suppressing Tumor PANoptosis

Advanced Science, EarlyView.
Tumor‐derived lactate establishes a metabolic lock that drives chemo‐immunotherapy resistance by suppressing PANoptosis. Mechanistically, KAT8 lactylates the mitochondrial translocator ANT2, which recruits PGAM5 to dephosphorylate CypD. This cascade restricts mitochondrial permeability transition pore opening, preventing pro‐inflammatory mtDNA leakage.
Sen Zhong, Wenlong Chen, Fanglong Liu, Shengyi Zhou, Bolin Yu, Yuying Wang, Xiqian Zhou, Xuehui Wang, Diya Liu, Zhuoyu Zhang, Xinran Wang, Mounia Lalouly, Yiwen Li, Zhefei Du, Tao Yan, Zhihui Xiao, Zhou Zhou, Huanhuan Zhu, Fengyuan Qian, Bowen Zheng, Lin Fang   +20 more
wiley   +1 more source

Drug repositioning for enzyme modulator based on human metabolite-likeness

BMC Bioinformatics, 2017
Background Recently, the metabolite-likeness of the drug space has emerged and has opened a new possibility for exploring human metabolite-like candidates in drug discovery.
Yoon Hyeok Lee, Hojae Choi, Seongyong Park, Boah Lee, Gwan-Su Yi   +4 more
doaj   +1 more source

PRMT5‐Dependent Stabilization of VPS34 Orchestrates Copper Trafficking to Shield Cancer Cells from Cuproptosis and Radiotherapy

Advanced Science, EarlyView.
Radioresistance arises partly from tumor cells evading cuproptosis via unknown defenses. This study reveals that the PRMT5‐VPS34 axis acts as a radiation‐activated anticuproptotic mechanism: PRMT5 methylates VPS34 at Arg174, recruiting USP10 to remove K48‐linked ubiquitination and prevent degradation.
Wei Chen, Ming‐Ying Xiao, Lan‐Lan Guo, Hao‐Yue Hu, Sui‐Xian Zhang, Bai‐Qiang Dong, Chen‐Fei Wu, Xia‐Hang Huang, Li Li, Run‐Zhe Chen, Yuan‐Yang Huang, Ying Jin, Hai Song, Ying Wang, Qi‐Wen Li, Ming Chen, Xuan Li, Yuan‐Yuan Chen   +17 more
wiley   +1 more source

Structure-based drug repositioning explains ibrutinib as VEGFR2 inhibitor.

PLoS ONE, 2020
Many drugs are promiscuous and bind to multiple targets. On the one hand, these targets may be linked to unwanted side effects, but on the other, they may achieve a combined desired effect (polypharmacology) or represent multiple diseases (drug ...
Melissa F Adasme, Daniele Parisi, Kristien Van Belle, Sebastian Salentin, V Joachim Haupt, Gary S Jennings, Jörg-Christian Heinrich, Jean Herman, Ben Sprangers, Thierry Louat, Yves Moreau, Michael Schroeder   +11 more
doaj   +1 more source

CXCL10/SLC11A1 Axis Exacerbates Septic Liver Injury by Regulating Neutrophil Extracellular Traps Formation to Drive Macrophage Pro‑Inflammatory Polarization

Advanced Science, EarlyView.
In sepsis‐induced liver injury, marked neutrophil infiltration correlates with disease severity. Neutrophil SLC11A1 drives intracellular Fe2+ and ROS via the Fenton reaction, promoting NETs formation. Hepatocyte‐derived CXCL10 recruits neutrophils and activates the JAK/STAT1/SLC11A1 axis, enhancing NETs‐mediated inflammation.
Haiping Lin, Shicong Zheng, Pei Song, Jie Chang, Zewei Chen, Cang Li, Min Yu, Lude Wang, Shian Yu   +8 more
wiley   +1 more source

TPI1 Loss Triggers a Metabolite‐Driven Mitochondrial Redox Vulnerability via the SARM1–cADPR–Ca2+ Axis

Advanced Science, EarlyView.
Metabolite‐driven redox stress governs cancer cell senescence. TPI1 deficiency elevates DHAP, initiating SARM1‐dependent cADPR‐Ca2+ release. Mitochondrial ROS surge subsequently induces DNA damage and senescence, offering a conserved therapeutic target in multiple cancers.
Chunyu Liu, Shun Wu, Chuang Wang, Zirui Zhou, Tianwei Cai, Wen Tao, Shidong Zuo, Chi Zhang, Yuhao Dong, Yi Feng, Qingbo Huang, Baojun Wang, Xin Ma, Haoli Ma, Xu Zhang, Yan Huang   +15 more
wiley   +1 more source

Drug Repositioning and Alzheimer's Disease [PDF]

, 2019
Drug repositioning er de seneste år begyndt at fylde mere inden for medicinudviklingen. Selvom drug repositioning ikke dækker over blot én metode, men derimod mange forskellige, har de alle dét fælles formål at udnytte noget af den viden, der allerede ...
Olufsen, Sarah Maria, Hansen, Caroline Pulz, Christiansen, Thea Emilie Bergmann, Andersen, Emma Sofie Ahrenkiel, Tang, Mikala Meling, Christensen, Lea Marie Juul   +5 more
core  

Chromatin Packing Domain Engineering Through the Manipulation of Nuclear Cationic States

Advanced Science, EarlyView.
Manipulation of intranuclear divalent cation concentrations rapidly and reversibly remodels chromatin packing domains in living cells. Magnesium depletion disrupts domain compaction, heterochromatin organization, and transcriptional regulation, whereas magnesium loading promotes more compact and stable domains.
Cody L. Dunton, Carrillo Paola Gonzalez, Luay Almassalha, Wing Shun Li, Ruyi Gong, Nicolas Acosta, I Chae Ye, Jane Frederick, Christopher Hogg, Saira John, J. A. Gareth Williams, Rikkert J. Nap, Igal Szleifer, Vadim Backman   +13 more
wiley   +1 more source