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• W2511344575 abstract "Mature neurotrophins as well as their pro forms are critically involved in the regulation of neuronal functions. They are signaling through three distinct types of receptors: tropomyosin receptor kinase family (TrkA/B/C), p75 neurotrophin receptor (p75(NTR)) and sortilin. Aberrant expression of p75(NTR) in the CNS is implicated in a variety of neurodegenerative diseases, including Alzheimer's disease. The goal of this work was to evaluate one of the very few reported p75(NTR) small molecule ligands as a lead compound for development of novel PET radiotracers for in vivo p75(NTR) imaging. Here we report that previously described ligand LM11A-24 shows significant inhibition of carbachol-induced persistent firing (PF) of entorhinal cortex (EC) pyramidal neurons in wild-type mice via selective interaction with p75(NTR). Based on this electrophysiological assay, the compound has very high potency with an EC50<10nM. We optimized the radiosynthesis of [(11)C]LM11A-24 as the first attempt to develop PET radioligand for in vivo imaging of p75(NTR). Despite some weak interaction with CNS tissues, the radiolabeled compound showed unfavorable in vivo profile presumably due to high hydrophilicity." @default.
• W2511344575 created "2016-09-16" @default.
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• W2511344575 date "2016-10-01" @default.
• W2511344575 modified "2023-10-17" @default.
• W2511344575 title "Towards the PET radiotracer for p75 neurotrophin receptor: [11C]LM11A-24 shows biological activity in vitro, but unfavorable ex vivo and in vivo profile" @default.
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• W2511344575 doi "https://doi.org/10.1016/j.bmc.2016.08.020" @default.
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