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Leveraging Structural and Computational Biology for Molecular Glue Discovery.
J Med Chem
January 2025
Experimental Drug Development Centre, Chromos, Agency for Science, Technology and Research, 10 Biopolis Road, #05-01, Singapore 138670.
The discovery of molecular glues has made significant strides, unlocking new avenues for targeted protein degradation as a therapeutic strategy, thereby expanding the scope of drug discovery into territories previously considered undruggable. Pioneering molecules like thalidomide and its derivatives have paved the way for the development of small molecules that can induce specific protein degradation by hijacking the cellular ubiquitin-proteasome system. Recent advancements have focused on expanding the range of E3 ligases and target proteins that can be modulated by molecular glues.
View Article and Find Full Text PDFLung-specific CRBN knockout attenuates influenza a virus-induced acute lung injury in mice: a potential therapeutic approach.
BMC Infect Dis
January 2025
State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
Influenza-related acute lung injury is a life-threatening condition primarily caused by uncontrolled replication of the influenza virus and intense proinflammatory responses. Cereblon (CRBN) is a protein known for its role in the ubiquitin-proteasome system and as a target of the drug thalidomide. However, the function of CRBN in influenza virus infection remains poorly understood.
View Article and Find Full Text PDFInhalation of crystalline silica particles causes silicosis, which is a severe inflammatory lung disease that is associated with granulomatous and fibrotic responses. We investigated whether silica-induced silicosis might promote airway hyperreactivity (AHR) and the role of TNF-α and thalidomide in this process. Mice received an intranasal instillation of silica particles (1.
View Article and Find Full Text PDFRadiation-Induced Brain Injury: Mechanistic Insights and the Promise of Gut-Brain Axis Therapies.
Brain Sci
December 2024
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Radiation therapy is widely recognized as an efficacious modality for treating neoplasms located within the craniofacial region. Nevertheless, this approach is not devoid of risks, predominantly concerning potential harm to the neural structures. Adverse effects may encompass focal cerebral necrosis, cognitive function compromise, cerebrovascular pathology, spinal cord injury, and detriment to the neural fibers constituting the brachial plexus.
View Article and Find Full Text PDFIdentifying novel aging-related diagnostic and prognostic models and aging-targeted drugs for sepsis patients.
Sci Rep
December 2024
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Sepsis is defined as a dysfunctional, life-threatening response to infection leading to multiorgan dysfunction and failure. During the past decade, studies have highlighted the relationship between sepsis and aging. However, the role of aging-related mechanisms in the progression and prognosis of sepsis remains unclear.
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