5-HT6R/FAAH modulator 2
5-HT6R/FAAH modulator 2 is a dual 5-HT6R antagonist and FAAH inhibitor with human 5-HT6R pKi 7.24, human FAAH pIC50 5.47, and blood-brain barrier penetration.5-HT6R/FAAH modulator 2 modulates serotonergic signaling, blocks 5-HT6R function, inhibits endocannabinoid degradation via FAAH catalytic activity suppression.5-HT6R/FAAH modulator 2 exhibits neuroprotective effects against mitochondrial dysfunction, amyloid-β, and glutamate-induced toxicity, reverses memory deficits.5-HT6R/FAAH modulator 2 shows reduced cytotoxicity relative to oxygen-containing lead compounds.5-HT6R/FAAH modulator 2 can be used for the research of Alzheimer's disease.
For research use only. We do not sell to patients.
- Formula: C26H34N6O3S
- Molecular Weight:510.65
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All 5-HT Receptor Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
5-HT6 Receptor |
In Vitro
5-HT6R/FAAH modulator 2 (Compound 4c) potently binds to and antagonizes human 5-HT6R with a pKi of 7.24 and pKb of 7.00, while moderately inhibiting human recombinant FAAH with a pIC50 of 5.47, and exhibits low affinity for off-target monoaminergic receptors[1].
5-HT6R/FAAH modulator 2 shows moderate metabolic stability in rat liver microsomes, with a half-life of 44 min and intrinsic clearance of 15.8 μL min−1·mg−1, and is metabolized primarily via sulfur oxidation[1].
5-HT6R/FAAH modulator 2 (0.8-20 μM; 1 h pre-incubation, 24 h co-incubation with okadaic acid) significantly preserves cell membrane integrity in okadaic acid-treated SH-SY5Y neuroblastoma cells[1].
5-HT6R/FAAH modulator 2 (10 μM) does not modulate β-amyloid aggregation[1].
5-HT6R/FAAH modulator 2 (10 μM; 1 h pre-incubation, 24 h co-incubation with glutamate) significantly protects HT-22 hippocampal neuronal cells from glutamate-induced toxicity, preserving membrane integrity and partially reducing caspase-3/7 activity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:SH-SY5Y neuroblastoma cells
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Concentration:0.8-20 μM
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Incubation Time:1 h pre-incubation; 24 h co-incubation with okadaic acid
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Result:Significantly reduced okadaic acid-induced cell membrane damage (cytotoxicity) compared to okadaic acid-treated cells, with statistical significance (p < 0.05) observed across doses.
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Cell Line:HT-22 hippocampal neuronal cells
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Concentration:10 μM
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Incubation Time:1 h pre-incubation; 24 h co-incubation with glutamate
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Result:Significantly preserved cell membrane integrity relative to glutamate-treated cells, showing a moderate protective effect.
Partially attenuated glutamate-induced caspase-3/7 activation, indicating reduced apoptotic cell death.
Chemical Information
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Molecular Weight 510.65
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Formula C26H34N6O3S
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SMILES
COC1=C(C(OC)=C(C=C1)CN2CCN(CC2)C3=NC(C(C)(SC4=CC=CC=C4)C)=NC(N)=N3)OC
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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Mitochondrial membrane-potential and mitochondrial mass staining
Mitochondrial membrane potential staining measures the electrochemical polarization across the mitochondrial inner membrane in live cells using lipophilic cationic fluorescent probes; early rhodamine-based work showed that selective mitochondrial dye accumulation is lost when the mitochondrial transmembrane potential is dissipated. JC-1 reports mitochondrial polarization by shifting from green monomer fluorescence to red J-aggregate fluorescence as dye concentration increases within energized mitochondria; therefore, the red/green fluorescence ratio is used as a relative readout of mitochondrial membrane potential. TMRE or TMRM staining provides a single-channel relative readout because these cationic rhodamine esters accumulate in polarized mitochondria, and lower fluorescence indicates reduced mitochondrial polarization when acquisition and dye-loading conditions are controlled. Mitochondrial mass staining is commonly performed with MitoTracker Green FM or related MitoTracker dyes as
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Amyloid: Congo Red Amyloid Staining
Congo red amyloid staining is a histochemical method used to detect extracellular amyloid deposits in tissue sections based on the affinity of Congo red dye for β-pleated sheet-rich protein aggregates. When bound to amyloid, Congo red produces characteristic apple-green birefringence under polarized light microscopy, which is widely regarded as a diagnostic feature of amyloid deposition in histopathology. The diagnostic principle relies on the combination of dye binding (congophilia) and optical anisotropy under polarized illumination, which distinguishes amyloid from most non-amyloid eosinophilic extracellular deposits in routine histological evaluation. Amyloid identification by Congo red staining remains a cornerstone in diagnostic pathology despite the availability of adjunct methods such as immunohistochemistry and mass spectrometry, particularly because of its ability to localize deposits directly within tissue architecture. The specificity of Congo red-positive deposits is incre
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Alzheimer’s Disease Modeling
Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive functions and loss of specific types of neurons and synapses. Alzheimer's symptoms can be simulated in mice by injecting drugs (such as Aβ) or genetically modified.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)