Screening and analysis of small molecules as potential PET ligands for brain imaging

Overview

This research program focuses on screening and analyzing small molecule candidates as potential PET ligands for brain imaging applications. The work targets the development of imaging agents capable of crossing the blood-brain barrier, achieving uniform distribution, and binding to specific targets including glycosylated proteins, lysosomal membrane proteins, and glycosaminoglycans. The research addresses a critical need in monitoring therapeutic effectiveness for lysosomal storage diseases and related neurological disorders through real-time PET imaging.

Technical specifications

The screening pipeline combines computational and experimental approaches:

• Virtual screening of molecules under 1000 Da, including peptides, pH-sensitive polymers, natural compounds, and derivatives from databases such as Supernatural II, IMPPAT, Chembank, ChemBL, PubChem, and ZINC
• EIIP/AQVN approach for evaluating target binding potential of screened molecules
• Molecular docking using AutoDock Vina to assess ligand-target interactions
• Molecular dynamic simulation to evaluate binding stability
• ADME/Toxicity analysis to characterize pharmacokinetic and safety profiles
• In vitro and in vivo validation including cytotoxicity assessment, blood-brain barrier crossing evaluation, steady-state distribution analysis, antigenicity testing, target binding and lysosomal co-localization studies, and effects on signaling pathways and adhesion

Technology readiness level

The research is at an early-to-mid stage of development. The computational screening workflow has been defined and the validation procedures are planned, covering both computational characterization and laboratory-based in vitro and in vivo testing. The work is positioned for collaborative research partnerships to advance ligand candidates through preclinical validation.