BuChE/FAAH-IN-1
BuChE/FAAH-IN-1 is an orally active and blood-brain barrier-permeable dual inhibitor of BuChE and FAAH, with IC50 values of 0.45 µM, 2.44 µM, and 0.17 µM against eqBuChE, hBuChE, and hFAAH, respectively. BuChE/FAAH-IN-1 exerts pseudo-irreversible inhibition through dynamic covalent modification of BuChE, and inhibits FAAH via a time-dependent, mixed-type non-competitive mechanism. BuChE/FAAH-IN-1 chelates metal ions such as Zn2+ and promotes cellular polarization from the M1 to the M2 phenotype (upregulating Arg-1 and CD206, and downregulating IL-1β and iNOS), thereby exerting neuroprotective and anti-neuroinflammatory effects. BuChE/FAAH-IN-1 can be used for research on Alzheimer's disease.
For research use only. We do not sell to patients.
- Formula: C23H26N2O5
- Molecular Weight:410.46
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
hBCHE 2.44 μM (IC50) |
eqBCHE 0.45 μM (IC50) |
hAChE 16.84 μM (IC50) |
EeAChE 9.35 μM (IC50) |
hFAAH 0.17 μM (IC50) |
CES1 2.45 μM (IC50) |
CES2 1.43 μM (IC50) |
iNOS |
IL-1β |
Arg-1 |
CD206 |
IL-6 |
TNF-α |
In Vitro
BuChE/FAAH-IN-1 (0.01-200 μM; 60 min) exhibits moderate inhibitory activity against hAChE and stronger inhibitory activity against hBuChE, with IC50 values of 16.84 μM and 2.44 μM, respectively[1].
BuChE/FAAH-IN-1 is a time-dependent hFAAH inhibitor; after 60-minute preincubation, its IC50 value decreases from 0.15 μM to 0.049 μM[1].
BuChE/FAAH-IN-1 (20 μM; 15 min) exhibits weak inhibitory activity against hMAGL, with an inhibition rate of 23.8% at 20 μM[1].
BuChE/FAAH-IN-1 (0.01-4 μM; 1-60 min) is a pseudo-irreversible hBuChE inhibitor with Kd = 0.38 μM[1].
BuChE/FAAH-IN-1 (10 min) inhibits CES1 and CES2 with IC50 values of 2.45 μM and 1.43 μM, respectively, and exhibits selectivity over hFAAH (SI of 14.4 and 8.38, respectively)[1].
BuChE/FAAH-IN-1 (50 μM; 30 min) exhibits strong chelating ability toward Zn2+, moderate chelating effect on Fe3+, and weak interaction with other tested metal ions[1].
BuChE/FAAH-IN-1 (25 μM; 24 h) exhibits good biocompatibility in HepG2, AML12, and PC12 cells, with cell viability above 80%[1].
BuChE/FAAH-IN-1 (12.5-100 μM; pretreatment for 1 h + co-culture for 24 h) is well tolerated by BV2 cells at 12.5 μM, produces slight toxicity at 25 μM, and reverses LPS (HY-D1056)-induced microglial morphological activation at 25 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HepG2, AML12, and PC12 cells
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Concentration:25 μM
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Incubation Time:24 h
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Result:Maintained cell survival rates above 80% in HepG2, AML12, and PC12 cells.
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Cell Line:PC12 cells
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Concentration:6.25, 12.5, 25, 50 μM
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Incubation Time:1 h (pretreatment); 24 h (H2O2 injury)
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Result:H2O2 alone reduced PC12 viability to 38.8%.
At 6.25 μM, weak protection was observed; across 12.5-50 μM, cell survival increased from 39.8% to 57.1%.
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Cell Line:BV2 microglial cells
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Concentration:12.5, 25, 50, 100 μM
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Incubation Time:1 h (pretreatment); 24 h (LPS stimulation)
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Result:At 12.5 μM, no significant effect on BV2 viability was observed; 25 μM caused a slight decrease; 50 and 100 μM markedly reduced viability.
At 25 μM, LPS-induced amoeboid morphological changes were significantly ameliorated.
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Cell Line:BV2 microglial cells
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Concentration:2.5, 5, 10 μM
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Incubation Time:1 h (pretreatment); 24 h (LPS stimulation)
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Result:Upregulated Arg-1 and CD206 (M2 markers) and inhibited iNOS and IL-1β (M1 markers) in a dose-dependent manner.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR (male, 6 weeks old, 18-24 g) (intracerebroventricular injection of Aβ1-42 peptide)[1]
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Dosage:2.5 mg/kg; 10 mg/kg
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Administration:i.g.; once daily; administration starting on day 3 after Aβ1-42 injection and continuing for 14 days
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Result:Ameliorated the exploratory behavior deficits and impaired spatial learning and memory abilities in Aβ1-42 model mice.
Reduced the abnormally deposited Aβ1-42 content in the brain tissue of model mice.
Alleviated neuronal atrophy and karyopyknosis in the hippocampus (especially the DG region), increased neuronal density, and caused no obvious liver toxicity during the experimental period.
Dose-dependently inhibited the abnormal activation of microglia (Iba-1) and astrocytes (GFAP) in the hippocampus, and significantly lowered the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in plasma, demonstrating a robust in vivo anti-neuroinflammatory effect.
Chemical Information
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Molecular Weight 410.46
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Formula C23H26N2O5
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SMILES
COC1=C(OC)C=C(CC(CC2CCN(C(OC3=NC=CC=C3)=O)CC2)C4=O)C4=C1
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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.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)