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Title:           Structure-based virtual screening, in vitro and in silico analysis identified novel potent m6A demethylase FTO inhibitors as promising neurotherapeutic agents
Subject:         European Journal of Medicinal Chemistry, 312 (2026) 118852. doi:10.1016/j.ejmech.2026.118852
Keywords:        Epigenetics,m6A,FTO inhibitors,Hit identification,Neurodegeneration,SAMP8
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      Title: Structure-based virtual screening, in vitro and in silico analysis identified novel potent m6A demethylase FTO inhibitors a ...
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        Title: 1 Introduction
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        Title: 2 Methodology
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          Title: 2.1 Structure-based virtual screening
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          Title: 2.2 PAMPA-BBB assay
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          Title: 2.3 Preparation of inhibitor solutions
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          Title: 2.4 FTO chemiluminescence assay kit
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          Title: 2.5 ALKBH5 chemiluminescence assay kit
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          Title: 2.6 Dataset preparation and 3D-QSAR pharmacophore generation
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          Title: 2.7 Molecular dynamics simulations
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          Title: 2.8 SH-SY5Y differentiation
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          Title: 2.9 Neuroprotection assay and cytotoxicity evaluation
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          Title: 2.10 hERG inhibition assay
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          Title: 2.12 Solubility assay
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          Title: 2.15 Open field test (OFT)
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          Title: 2.16 Object location test (OLT)
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          Title: 2.17 Novel object recognition test (NORT)
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          Title: 2.18 Isolation of the tissues
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          Title: 2.19 RNA extraction and determination of gene expression
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          Title: 2.20 Quantification of m6A RNA methylation
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          Title: 2.21 Statistical analysis
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          Title: 3.1 Identification of novel FTO inhibitors through structure-based virtual screening
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          Title: 3.2 In vitro BBB penetration study
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          Title: 3.3 In vitro determination of FTO inhibition activity
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          Title: 3.4 In vitro selectivity over ALKBH5 inhibition
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          Title: 3.5 3D-QSAR mapping of selected hits
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          Title: 3.6 Molecular modelling and MD simulations
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          Title: 3.7 DMPK profiling of selected novel FTO inhibitors
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          Title: 3.9 In vivo pharmacokinetic profile of selected FTO inhibitors
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          Title: 3.10 Compound VI ameliorates cognitive deficits in SAMP8 mice
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        Title: Funding
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        Title: CRediT authorship contribution statement
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        Title: Declaration of competing interest
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        Title: Appendix A Supplementary data
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        Title: Data availability
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        Title: References
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   Type: CRC32
  Checksum: 11a8f53b01f2ca66326702fa7141b9ba
   Type: MD5
  Checksum: d4fec0dd44c20f2a0df02254b0e0a4724611c207
   Type: SHA-1
  Checksum: b651ba46b5ba2b66758bbebea858346a28d197493e9c4cb34d2d6394fb46e46a
   Type: SHA-256