1. Neuronal Signaling
  2. Cholinesterase (ChE)
  3. AChE/BChE-IN-35

AChE/BChE-IN-35, Tacrine (HY-111338) derivative, is a brain-penetrant dual AChE/BChE inhibitor with an Electric Eel AChE IC50 of 123.66 nM, human AChE IC50 of 122.34 nM, and equine BChE IC50 of 488.00 nM. AChE/BChE-IN-35 undergoes LAT1-mediated active transport across cell membranes. AChE/BChE-IN-35 exhibits enhanced brain exposure with slower brain tissue elimination. AChE/BChE-IN-35 can be used for the research of alzheimer's disease.

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AChE/BChE-IN-35

AChE/BChE-IN-35 Chemical Structure

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Description

AChE/BChE-IN-35, Tacrine (HY-111338) derivative, is a brain-penetrant dual AChE/BChE inhibitor with an Electric Eel AChE IC50 of 123.66 nM, human AChE IC50 of 122.34 nM, and equine BChE IC50 of 488.00 nM. AChE/BChE-IN-35 undergoes LAT1-mediated active transport across cell membranes. AChE/BChE-IN-35 exhibits enhanced brain exposure with slower brain tissue elimination. AChE/BChE-IN-35 can be used for the research of alzheimer's disease[1].

IC50 & Target[1]

hAChE

122.34 nM (IC50)

electric eel AChE

123.66 nM (IC50)

eqBCHE

488.00 nM (IC50)

In Vitro

AChE/BChE-IN-35 (Compound L3) (5 min) inhibits eeAChE, hAChE, and eqBChE with IC50 values of 123.66 nM, 122.34 nM, and 488.00 nM, respectively[1].
AChE/BChE-IN-35 (50-100 μM; 24 h) shows low cytotoxicity toward bEnd.3 cells, with viability remaining close to 80% after 24 h treatment at 100 μM[1].
AChE/BChE-IN-35 (5 μg/mL; 30-300 min) crosses an in vitro bEnd.3 cell blood-brain barrier model with an apparent permeability coefficient of 11.25 × 10-6 cm/s[1].
AChE/BChE-IN-35 (4 h) is transported into U87 cells via LAT1, as shown by undetectable intracellular levels in the presence of an LAT1 competitive inhibitor[1].
AChE/BChE-IN-35 (10-50 μM; 24 h) shows low cytotoxicity toward HBMEC, BV2, PC-12, SH-SY5Y, with viability remaining above 50% at tested concentrations after 24 h treatment[1].
AChE/BChE-IN-35 (10-100 μM; 24 h) shows low hepatotoxicity in HepG2 and L02 cells, with viability remaining above 50% at tested concentrations after 24 h treatment[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Cytotoxicity Assay[1]

Cell Line: mouse brain microvascular endothelial cells (bEnd.3)
Concentration: 50, 100 μM
Incubation Time: 24 h
Result: Maintained cell viability close to 80% at 100 μM.
Maintained cell viability nearly 100% at 50 μM.

Cell Cytotoxicity Assay[1]

Cell Line: human brain microvascular endothelial cells (HBMEC), murine microglial cells (BV2), rat adrenal pheochromocytoma cells (PC-12), human neuroblastoma cells (SH-SY5Y), human normal hepatocyte (L02), human hepatocellular carcinoma cells (HepG2)
Concentration: 10, 20, 50, 100 μM (HBMEC, BV2, PC-12, SH-SY5Y); 1.25, 2.5, 5, 10, 20, 50, 100, 200 μM (HepG2, L02)
Incubation Time: 24 h
Result: Maintained viability above 50% across 10-50 μM in HBMEC, BV2, PC-12, and SH-SY5Y cells.
Maintained viability above 50% across 10-100 μM in HepG2 and L02 cells.
Parmacokinetics
Species Dose Route AUC Brain-to-Plasma Ratio Tmax
Mice[1] 10 mg/kg i.p. 20037 min·ng/mL 68 % 15 min
In Vivo

AChE/BChE-IN-35 (Compound L3) (10 mg/kg; i.p.; single dose) exhibits stronger blood-brain barrier permeability than Tacrine (HY-111338), with a brain-to-plasma AUC0-t ratio of 0.68 and 21.3% higher total brain exposure[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

446.54

Formula

C26H30N4O3

SMILES

OC([C@H](N)CC1=CC(C(NCCCNC2=C3C(C=CC=C3)=NC4=C2CCCC4)=O)=CC=C1)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation
References
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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AChE/BChE-IN-35
Cat. No.:
HY-182254
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