Latrepirdine dihydrochloride
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Latrepirdine dihydrochloride is a neuroactive compound with antagonist activity at histaminergic, α-adrenergic, and serotonergic receptors. Latrepirdine stimulates amyloid precursor protein (APP) catabolism and amyloid-β (Aβ) secretion.
For research use only. We do not sell to patients.
- Purity: 99.65%
- CAS No.: 97657-92-6
- Formula: C21H27Cl2N3
- Molecular Weight:392.37
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Storage:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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Biological Activity
Amyloid-β (Aβ), Histaminergic receptor, α-adrenergic receptor, Serotonergic receptor[1]
Latrepirdine has been reported to possess several properties that are potentially relevant to the treatment of neurodegenerative diseases: (1) protection of cultured cells from the cytotoxicity of amyloid-β (Aβ) peptide; (2) stabilization of mitochondrial function and calcium homeostasis; (3) modulation of Aβ release from cultured cells, isolated intact nerve terminals, and from hippocampal neurons in living mouse brain; and (4) promotion of neurogenesis in the murine hippocampus. Treatment of cultured mammalian cells with Latrepirdine leads to enhanced mTOR- and Atg5-dependent autophagy. Latrepirdine modulates Atg5-dependent autophagic activity in a dose-dependent manner and via the mTOR-signaling pathway. HeLa cells stably expressing LC3 fused are treated with EGFP (eGFP-LC3) for 3 or 6 hours in the absence or presence of 50 μM Latrepirdine. Treatment with Latrepirdine for 3 or 6 hours markedly enhances the number of eGFP-LC3 punctae, indicating that Latrepirdine induces formation of autophagosomes. Next, mouse N2a neuroblastoma cells are treated in the absence (vehicle) or presence of 5 nM, 500 nM or 50 μM Latrepirdine for 3 or 6 hours in order to determine the effects of acute drug treatment on the regulation of autophagy. A significant and dose-dependent increase is observed in LC3-II levels in N2a cells following 3- or 6-hour treatment with either 500 nM or 50 μM Latrepirdine. A significant decrease of p-mTOR and p-S6K from N2a cells treated with 50 μM Latrepirdine for 3 hours is observed, whereas the total mTOR and p70S6K levels remain relatively constant[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 97657-92-6
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Appearance Solid
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Molecular Weight 392.37
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Formula C21H27Cl2N3
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Color White to khaki
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SMILES
CN(C1)CCC2=C1C3=CC(C)=CC=C3N2CCC4=CN=C(C)C=C4.Cl.Cl
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Synonyms
Dimebolin dihydrochloride
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
H2O : 100 mg/mL (254.86 mM; Need ultrasonic)
DMSO : 6.4 mg/mL (16.31 mM; Need warming; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 0.5 mg/mL (1.27 mM); Clear solution
This protocol yields a clear solution of ≥ 0.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (5.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 0.5 mg/mL (1.27 mM); Clear solution
This protocol yields a clear solution of ≥ 0.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (5.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: PBS
Solubility: 100 mg/mL (254.86 mM); Clear solution; Need ultrasonic
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
Protocol
N2a cells, stable human cervical carcinoma (HeLa) cells expressing EGFP-LC3, and mouse embryonic fibroblasts (MEFs) derived from wildtype mice or ATG5-/- mice are maintained in “growth medium” (high glucose Dulbecco's modified Eagle's medium supplemented with 10% FBS and 100 units/mL Penicillin/Streptomycin) at 37°C, 5% CO2. N2a cells stably transfected with APPK670N, M671L are maintained in growth medium supplemented with 0.2 mg/mL G418. Cells are washed 1× with ice cold PBS (pH 7.4) then incubated with either Latrepirdine (5 nM, 500 nM or 50 μM) or vehicle (growth medium). Following 3-, 6-, or 24-hour of treatment, cells are washed 1x with ice cold PBS, and collected in lysis buffer (50 mM Tris-HCl, 150 mM NaCl, 1 mM Pepstatin, 1 mM PMSF, 1% Triton X-100, EDTA-free mini-complete protease inhibitor cocktail tablet) then centrifuged (14,000 RPM) for 15 minutes at 4°C. For time-course experiments, cells are washed 2× with ice-cold PBS (pH 7.4) and incubated for the indicated time in serum-free DMEM containing 50 μg/mL CHX or 50 μg/mL Cycloheximide (CHX)+50 μg/mL Chloroquine (CQ). Baseline (T0) samples are collected immediately prior to treatment[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice[1]
Male 53-55-day-old TgCRND8 mice (N=25) are randomly distributed into either of the two treatment groups: Latrepirdine (n=13 TgCRND8) or vehicle (n=12 TgCRND8). Animals receive 21 consecutive once daily intraperitoneal injections of either 3.5 mg/kg Latrepirdine or 0.9% saline (vehicle). 90-day-old male TgCRND8 mice (N=28) or their wild-type littermates (N=56) are randomly distributed into either of two treatment groups: Latrepirdine (n=13 TgCRND8; n=21 nTg) or vehicle (n=15 TgCRND8; n=25 nTg). Following treatment, animals are sacrificed and transcardially perfused with ice-cold PBS (pH 7.4). Male 90-day-old (n=5 per genotype) or 120-day-old (n=6 per genotype) TgCRND8 mice or their non-transgenic littermates are sacrificed and transcardially perfused with ice-cold PBS (pH 7.4). One hemisphere from each mouse is post-fixed in 4% paraformaldeyhde in PBS (pH 7.4) for histological analysis and the other hemisphere is dissected and snap-frozen for biochemical analysis.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (280 KB)
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SDS (418 KB)
- English - EN (418 KB)
- Français - FR (418 KB)
- Deutsch - DE (418 KB)
- Norwegian - NO (418 KB)
- Español - ES (418 KB)
- Swedish - SV (418 KB)
- Italian - IT (418 KB)
- Korean - KR (418 KB)
- Portuguese - PT (418 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO / H2O | 1 mM | 2.5486 mL | 12.7431 mL | 25.4861 mL | 63.7154 mL |
| 5 mM | 0.5097 mL | 2.5486 mL | 5.0972 mL | 12.7431 mL | |
| 10 mM | 0.2549 mL | 1.2743 mL | 2.5486 mL | 6.3715 mL | |
| 15 mM | 0.1699 mL | 0.8495 mL | 1.6991 mL | 4.2477 mL | |
| H2O | 20 mM | 0.1274 mL | 0.6372 mL | 1.2743 mL | 3.1858 mL |
| 25 mM | 0.1019 mL | 0.5097 mL | 1.0194 mL | 2.5486 mL | |
| 30 mM | 0.0850 mL | 0.4248 mL | 0.8495 mL | 2.1238 mL | |
| 40 mM | 0.0637 mL | 0.3186 mL | 0.6372 mL | 1.5929 mL | |
| 50 mM | 0.0510 mL | 0.2549 mL | 0.5097 mL | 1.2743 mL | |
| 60 mM | 0.0425 mL | 0.2124 mL | 0.4248 mL | 1.0619 mL | |
| 80 mM | 0.0319 mL | 0.1593 mL | 0.3186 mL | 0.7964 mL | |
| 100 mM | 0.0255 mL | 0.1274 mL | 0.2549 mL | 0.6372 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.