Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Alzheimer's disease (AD) is a complex neurodegenerative disorder having limited treatment options. The beta-site APP cleaving enzyme 1 (BACE-1) is a key target for therapeutic intervention in Alzheimer's disease. To discover new scaffolds for BACE-1 inhibitors, a ChemBridge DIVERSet library of 20,000 small molecules was employed to structure-based virtual screening. The top 45 compounds, based on docking scores and binding affinities, were tested for BACE-1 inhibitory activity using a FRET assay. Four compounds, 18 (5353320), 20 (5262831), 29 (5784196) and 32 (5794006) demonstrated more than 35 % inhibitory activity at 10 μM. Notably, pyrazole-5-carbohydrazide 29 (5784196) exhibited BACE-1 inhibition with an IC value of 14.5 μM and a ki value of 0.25 μM. Additionally, it also inhibits the self-aggregation of β-amyloid, with IC value of 14.87 μM. Molecular modeling and dynamics simulations provided insights into its interaction pattern and stability of the enzyme-inhibitor complex. These findings suggest that virtual screening is an efficient and cost-effective method for identifying potential leads for AD.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/cmdc.202400685 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Acclimatising with 3D virtual reality video improves simulator performance: initial findings of a randomised controlled feasibility trial.
Surg Endosc
September 2025
Department of Surgery & Interventional Science, University College London, Gower St, London, WC1E 6BT, UK.
Introduction: The transition from traditional laparoscopy to robotic surgery marks a significant chage in surgical practice. An understated aspect of this transition may be the three dimensional (3D) view from the surgical console. This study hypothesises that acclimatisation with 3D virtual reality (VR) video may enhance robotic simulator performance in novice robotic surgeons.
View Article and Find Full Text PDFAntiemetic drug fosaprepitant exerts anti-tumor effects against NSCLC by targeting FAK to inhibit AKT and JNK/c-Jun pathways.
Acta Pharmacol Sin
September 2025
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Non-small cell lung cancer (NSCLC) is an aggressive malignancy with a poor prognosis. Abnormal expression of focal adhesion kinase (FAK) is closely linked to NSCLC progression, highlighting the need for effective FAK inhibitors in NSCLC treatment. In this study we conducted high-throughput virtual screening combined with cellular assays to identify potential FAK inhibitors for NSCLC treatment.
View Article and Find Full Text PDFExperiences and user perceptions of virtual-reality-based mindfulness interventions: protocol for a systematic review and thematic synthesis.
BMJ Open
September 2025
Medical Affairs - Research Innovation & Enterprise, Alexandra Hospital, National University Health System, Alexandra Hospital, Singapore.
Introduction: Virtual reality (VR) technology is increasingly being explored as a medium for delivering mindfulness-based interventions. While studies have investigated the feasibility and efficacy of VR-based mindfulness interventions, there has been limited synthesis of user experiences and perceptions across diverse applications, hindering the iterative refinement of these technologies and limiting evidence-based guidance for effective deployment in real-world settings. This systematic review aims to comprehensively identify, appraise and synthesise qualitative research on end-user experiences and perceptions of VR-based mindfulness interventions.
View Article and Find Full Text PDFA National Cancer Database analysis of the clinicopathologic characteristics and outcomes of appendiceal neuroendocrine tumors.
Surgery
September 2025
Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL. Electronic address:
Introduction: Appendiceal neuroendocrine neoplasms are rare lesions which are generally incidentally discovered during or after appendectomies. Recent advances have refined their classification and improved diagnostic rates, highlighting their distinct pathologic and clinical presentations. The present study aimed to assess the characteristics and outcomes of appendiceal neuroendocrine neoplasms using data from the U.
View Article and Find Full Text PDFThe causal journey: from maps to mechanisms and digital twins.
Cereb Cortex
August 2025
Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale, Institut de Neurosciences des Systèmes (INS) UMR1106, Marseille 13005, France.
Over three decades, statistical parametric mapping has transformed neuroimaging from descriptive mapping to causal inference, placing generative models at the core of causal explanations for brain function. It inspired to a large degree The Virtual Brain, which builds subject-specific digital twins from multimodal data, enabling brain simulations and exploration. Both frameworks converge at parameter estimation, where model and data meet, providing the mathematical manifestation of cause-effect in pathophysiology.
View Article and Find Full Text PDF