ArticleMolecular imaging and biology2023
Identification of a Putative α-synuclein Radioligand Using an in silico Similarity Search.
Article in Molecular imaging and biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- PET imaging of alpha-synuclein: from radiotracer design through in vitro and in vivo translation.European journal of nuclear medicine and molecular imaging · 2026Review
- Machine learning prediction of multiple distinct high-affinity chemotypes for α-synuclein fibrils.Chemical communications (Cambridge, England) · 2026Article
- Advances in PET imaging of protein aggregates associated with neurodegenerative disease.Nature reviews. Neurology · 2025Review
- Alpha-synuclein fibril structures cluster into distinct classes.Biophysical journal · 2025Review
- Development of Positron Emission Tomography Radiotracers for Imaging α-Synuclein Aggregates.Cells · 2025Review
- Strategic Modulation of Polarity and Viscosity Sensitivity of Bimane Molecular Rotor-Based Fluorophores for Imaging α-Synuclein.Journal of the American Chemical Society · 2025Article
- PET tracer development for imaging α-synucleinopathies.Archives of pharmacal research · 2025Review
- Binding adaptability of chemical ligands to polymorphic α-synuclein amyloid fibrils.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Novel Brain PET Radiotracer for Imaging Alpha Synuclein Fibrils in Multiple System Atrophy.Journal of medicinal chemistry · 2023Article
- Research progress in brain-targeted nasal drug delivery.Frontiers in aging neuroscience · 2023Review
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Authors and funding
18 authors at 2 institutions in 1 country.
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Abstract
purposePrevious studies from our lab utilized an ultra-high throughput screening method to identify compound 1 as a small molecule that binds to alpha-synuclein (α-synuclein) fibrils. The goal of the current study was to conduct a similarity search of 1 to identify structural analogs having improved in vitro binding properties for this target that could be labeled with radionuclides for both in vitro and in vivo studies for measuring α-synuclein aggregates.
methodsUsing 1 as a lead compound in a similarity search, isoxazole derivative 15 was identified to bind to α-synuclein fibrils with high affinity in competition binding assays. A photocrosslinkable version was used to confirm binding site preference. Derivative 21, the iodo-analog of 15, was synthesized, and subsequently radiolabeled isotopologs [
resultsIn silico molecular docking and molecular dynamic simulation studies for a panel of compounds identified through a similarity search, were shown to correlate with K
conclusionThrough a relatively simple ligand-based similarity search, we identified a new radioligand that binds with high affinity (<10 nM) to α-synuclein fibrils and PD tissue. Although the radioligand has suboptimal selectivity for α-synuclein towards Aβ and high non-specific binding, we show here that a simple in silico approach is a promising strategy to identify novel ligands for target proteins in the CNS with the potential to be radiolabeled for PET neuroimaging studies.
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