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Multi-CADD Method Screening of NCEs that are CNS-penetrant, modulate neuroinflammation, and enhance synaptic plasticity.​

Background

Alzheimer’s disease is a major neurodegenerative condition with limited effective treatments. The goal is to find new chemical entities (NCEs) that are CNS-penetrant, modulate neuroinflammation, and enhance synaptic plasticity.​

Question of Interest

Can we identify CNS-penetrant compounds that effectively target Alzheimer’s disease mechanisms?​

Methods

A library of 50,000 compounds was screened. ADME profiling ensured CNS penetration, followed by toxicity screening for safety. molecular docking assessed compound-target interactions, and molecular dynamics (MD) simulations predicted their stability and behavior.​

Results

Six lead compounds were identified from 50,000 screened, showing CNS penetration and efficacy in modulating neuroinflammation and synaptic plasticity.​  

Impact

  • 6 Leads were generated, synthesized, and selected for further in vitro evaluation.​
  • This approach can be applied to other CNS diseases, offering a robust framework for drug discovery.​

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