(-)-P7C3-S243
(-)-P7C3-S243 is an orally active, blood-brain barrier permeable neuroprotective agent. (-)-P7C3-S243 binds to μ-opioid Receptor and TSPO. (-)-P7C3-S243 inhibits the premature apoptosis death of newborn hippocampal neurons, protects mature nigral dopaminergic neurons, promotes neuronal survival and prevents cognitive impairment. (-)-P7C3-S243 ameliorates depression-like behaviors in rat models. (-)-P7C3-S243 is applicable to research related to Parkinson's disease and Alzheimer's disease.
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- CAS No.: 1597443-57-6
- 화학식: C21H18Br2FN3O
- 분자량:507.19
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- 순도&문서
- References
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All Opioid Receptor Isoforms
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Biological Activity
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Cell Line
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Type | Value | Description | References |
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| HCC44 | IC50 |
10 μM
Compound: (-)-(S)-15, (-)-P7C3-S243
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Cytotoxicity against human HCC44 cells
Cytotoxicity against human HCC44 cells
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[PMID: 24697290] |
(-)-P7C3-S243 (Compound 15) weakly inhibits CYP1A2 (IC50 = 20 μM) and CYP2C19 (IC50 = 1.9 μM) in vitro, but shows no inhibitory effect on multiple other tested CYP subtypes[1].
(-)-P7C3-S243 binds to the μ-opioid receptor (IC50 = 8.2 μM) and TSPO (IC50 = 0.35 μM) in vitro, but does not bind to most other tested neuronal receptors and channels[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
(-)-P7C3-S243 (1-10 mg/kg; i.p.; twice daily for 21 consecutive days) dose-dependently protects mature dopaminergic neurons in the substantia nigra of mice treated with MPTP (HY-15608)[1].
(-)-P7C3-S243 (10 mg/kg; i.p.; 10 days) doubles the level of postnatal hippocampal neurogenesis in TgF344-AD rats, protects the rats from early depression-like behaviors and late cognitive impairment, reduces neurodegeneration and neuronal loss, and also ameliorates age-related depression-like behaviors in wild-type rats[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/J6 (12-week-old)[1]
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Dosage:10 μM; 0.1-10 mg/kg/day
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Administration:i.c.v.; 0.5 μL/h; 7 days; i.p.; BID; 7 days
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Result:Approximately doubled the number of surviving BrdU+ newborn hippocampal neurons compared to vehicle-treated mice.
Showed a smooth dose-response curve, with activity detectable at 1 mg/kg/day and maximum efficacy achieved at 10 mg/kg/day; efficacy reflected increased survival of newborn hippocampal neurons via neuroprotection (not increased proliferation).
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Animal Model:C57Bl/6 (adult male; MPTP-induced Parkinson's disease)[1]
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Dosage:1, 3, 5, 10 mg/kg/day
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Administration:i.p.; BID; 21 days
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Result:Showed significant neuroprotective activity at 1 mg/kg/day, and at the highest tested dose of 10 mg/kg/day, rescued over 85% of TH+ dopaminergic neurons in the substantia nigra (compared to MPTP-treated vehicle controls).; Demonstrated higher efficacy than that of P7C3-A20, with strict enantiomeric specificity (only the (−)-S enantiomer was active).
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Animal Model:Fischer 344 rats (male and female, 6 months old at treatment initiation; TgF344-AD transgenic overexpressing human mutant APP_SW and PS1ΔE9 genes; wild-type)[2]
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Dosage:10 mg/kg/d
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Administration:daily; 9 months (15-month assessments); 18 months (24-month assessments)
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Result:Reduced time spent immobile in the Porsolt forced swim test in TgF344-AD rats to levels comparable to WT animals at 15 months.
Did not affect locomotor activity or cause cognitive deficits in any group at 15 months.
Improved performance in the Morris water maze reversal memory probe in TgF344-AD rats, reducing time to locate the target position to levels similar to WT animals at 24 months.
Ameliorated depression-like behavior in 24-month-old WT rats, reducing time spent immobile in the Porsolt forced swim test from mean 45 seconds to mean 20 seconds (p=0.0176), but did not correct depression-like behavior in 24-month-old TgF344-AD rats.
Significantly reduced vacuole formation in the hippocampus and cerebral cortex of TgF344-AD rats at 24 months.
Prevented neuronal cell loss in the hippocampus and cerebral cortex, and increased neuronal cell counts in the dentate gyrus granule cell layer of TgF344-AD rats at 24 months.
Did not alter amyloid plaque deposition, levels of soluble or insoluble Aβ1-40/Aβ1-42 peptides, tau hyperphosphorylation (Tau PS199/202), or glial activation (GFAP+ astrocytes or Iba1+ microglia) in TgF344-AD rats at 24 months.
Chemical Information
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CAS No. 1597443-57-6
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분자량 507.19
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화학식 C21H18Br2FN3O
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SMILES
F[C@@H](CNC1=NC(OC)=CC=C1)CN2C3=CC=C(Br)C=C3C4=C2C=CC(Br)=C4
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
[1]. Naidoo J, et al. Discovery of a neuroprotective chemical, (S)-N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [(-)-P7C3-S243], with improved druglike properties. J Med Chem. 2014;57(9):3746-3754. [Content Brief]
[2]. Voorhees JR, et al. (-)-P7C3-S243 Protects a Rat Model of Alzheimer's Disease From Neuropsychiatric Deficits and Neurodegeneration Without Altering Amyloid Deposition or Reactive Glia. Biol Psychiatry. 2018;84(7):488-498. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
(-)-P7C3-S243 Related Classifications
HY-186105A Related Classifications
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