ArticleACS medicinal chemistry letters2015
Synthesis and Initial in Vivo Studies with [(11)C]SB-216763: The First Radiolabeled Brain Penetrative Inhibitor of GSK-3.
Article in ACS medicinal chemistry letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
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- Radiosynthesis and Evaluation ofACS pharmacology & translational science · 2025Article
- Synthesis and preliminary evaluation of novel PET probes for GSK-3 imaging.Scientific reports · 2024Article
- Radiosynthesis and evaluation of a novelAmerican journal of nuclear medicine and molecular imaging · 2024Article
- In Vivo Imaging and Kinetic Modeling of Novel Glycogen Synthase Kinase-3 Radiotracers [Pharmaceuticals (Basel, Switzerland) · 2023Article
- PET imaging of glycogen synthase kinase-3 in pancreatic cancer xenograft mouse models.American journal of nuclear medicine and molecular imaging · 2022Article
- The Repertoire of Small-Molecule PET Probes for Neuroinflammation Imaging: Challenges and Opportunities beyond TSPO.Journal of medicinal chemistry · 2021Review
- Radiofluorination of oxazole-carboxamides for preclinical PET neuroimaging of GSK-3.Journal of fluorine chemistry · 2021Article
- Glycogen Synthase Kinase-3 Inhibitors: Preclinical and Clinical Focus on CNS-A Decade Onward.Frontiers in molecular neuroscience · 2021Review
- FGF20 Protected Against BBB Disruption After Traumatic Brain Injury by Upregulating Junction Protein Expression and Inhibiting the Inflammatory Response.Frontiers in pharmacology · 2020Article
- Clinically Precedented Protein Kinases: Rationale for Their Use in Neurodegenerative Disease.Frontiers in aging neuroscience · 2020Review
- Radiosynthesis and in Vivo Evaluation of [ACS chemical neuroscience · 2017Article
- Development of [ACS medicinal chemistry letters · 2017Article
- Article
- Discovery of a Highly Selective Glycogen Synthase Kinase-3 Inhibitor (PF-04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging.Angewandte Chemie (International ed. in English) · 2016Article
- Synthesis of Diverse (11)C-Labeled PET Radiotracers via Direct Incorporation of [(11)C]CO2.Bioconjugate chemistry · 2016Article
- Synthesis and Evaluation of [(18)F]RAGER: A First Generation Small-Molecule PET Radioligand Targeting the Receptor for Advanced Glycation Endproducts.ACS chemical neuroscience · 2016Article
- Glycogen Synthase Kinase-3 (GSK-3)-Targeted Therapy and Imaging.Theranostics · 2016Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Quantifying glycogen synthase kinase-3 (GSK-3) activity in vivo using positron emission tomography (PET) imaging is of interest because dysregulation of GSK-3 is implicated in numerous diseases and neurological disorders for which GSK-3 inhibitors are being considered as therapeutic strategies. Previous PET radiotracers for GSK-3 have been reported, but none of the published examples cross the blood-brain barrier. Therefore, we have an ongoing interest in developing a brain penetrating radiotracer for GSK-3. To this end, we were interested in synthesis and preclinical evaluation of [(11)C]SB-216763, a high-affinity inhibitor of GSK-3 (K i = 9 nM; IC50 = 34 nM). Initial radiosyntheses of [(11)C]SB-216763 proved ineffective in our hands because of competing [3 + 3] sigmatropic shifts. Therefore, we have developed a novel one-pot two-step synthesis of [(11)C]SB-216763 from a 2,4-dimethoxybenzyl-protected maleimide precursor, which provided high specific activity [(11)C]SB-216763 in 1% noncorrected radiochemical yield (based upon [(11)C]CH3I) and 97-100% radiochemical purity (n = 7). Initial preclinical evaluation in rodent and nonhuman primate PET imaging studies revealed high initial brain uptake (peak rodent SUV = 2.5 @ 3 min postinjection; peak nonhuman primate SUV = 1.9 @ 5 min postinjection) followed by washout. Brain uptake was highest in thalamus, striatum, cortex, and cerebellum, areas known to be rich in GSK-3. These results make the arylindolemaleimide skeleton our lead scaffold for developing a PET radiotracer for quantification of GSK-3 density in vivo and ultimately translating it into clinical use.
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