LH2-051
Based on 1 Customer Validation
LH2-051, a lysosome-enhancing compound (LYEC), is a brain-penetrant dopamine transporter (DAT) inhibitor (Ki: 0.95 μM). LH2-051 inhibits DAT-mediated dopamine uptake with an IC50 of 3.0 μM. LH2-051 promotes nuclear translocation of TFEB and lysosome biogenesis. LH2-051 improves the memory of amyloid precursor protein (APP)/Presenilin 1 (PS1) mice. LH2-051 can be used for the study of Alzheimer’s disease.
For research use only. We do not sell to patients.
- Purity : 99.85%
- CAS No.: 2358754-22-8
- Formula: C27H34N2O3
- Molecular Weight:434.57
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Storage:
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
In Vitro
LH2-051 (3-50 μM, 3-12 h) promotes nuclear translocation of TFEB which is independent of inactivation of mTORC1 or GSK3β[1].
LH2-051 (10-4-10-1 μM) binds directly to DAT (Ki = 0.95 μM) and inhibits DAT-mediated dopamine uptake with an IC50 of 3.0 μM in HEK293 cells[1].
LH2-051 (30 μM, 0-6 h) promotes lysosome biogenesis in HeLa cells and SH-SY5Y cells, which is regulated by CDK9-mediated phosphorylation of TFEB[1].
LH2-051 (30 μM, 3 h) induces the translocation of DAT from the plasma membrane onto lysosomal membranes in SH-SY5Y cells[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:HeLa cells and SH-SY5Y cells
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Concentration:3, 5, 10, 30, 50 μM
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Incubation Time:3, 6 h
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Result:Promoted the nuclear translocation of TFEB-EGFP in a dose- and time-dependent manner.
Enhanced the staining and protein level of endogenous lysosomal-associated membrane protein 1 (LAMP1).
Enhanced the staining of Boron dipyrromethene difluoride (BODIPY) pepstatin A, which binds to active cathepsin D inside lysosomes.
Promoted translocation of endogenous DAT to lysosomes, and release of both endogenous CDK9 and endogenous TFEB from lysosomes.
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Cell Line:HeLa cells
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Concentration:30 μM
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Incubation Time:6 h
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Result:Induced translocation of endogenous TFEB from the cytosol into the nucleus.
Did not inhibit mTORC1 activity.
Did not significantly affect GSK3β phosphorylation at Ser9.
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Cell Line:HeLa cells and TFEB KO cells
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Concentration:30 μM
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Incubation Time:12 h
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Result:Increased the expression of lysosomal and autophagic genes which was dependent on TFEB. protein 1 (LAMP1).
Enhanced the staining of Boron dipyrromethene difluoride (BODIPY) pepstatin A, which binds to active cathepsin D inside lysosomes.
Promoted translocation of endogenous DAT to lysosomes, and release of both endogenous CDK9 and endogenous TFEB from lysosomes.
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Cell Line:SH-SY5Y cells
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Concentration:30 μM
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Incubation Time:1, 2, 3, 6 h
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Result:Reduced the phosphorylation of Rpb1.
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:Five-month-old APP/PS1 mice (male)[1]
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Dosage:10 mg/kg
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Administration:i.p. once daily for 30 days
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Result:Reduced Aβ load by 63.2% in the cortex and 65.6% in hippocampus compared with age-matched vehicle-injected controls.
Upregulated the expression of lysosomal and autophagic genes in APP/PS1 mouse brains.
Took significantly less time to locate the hidden platform and landed on the platform more often when compared to vehicle-injected controls during the training trial.
Enhanced lysosome biogenesis and Aβ clearance in APP/PS1 mice, and improved their learning, memory, and cognitive function.
Chemical Information
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CAS No. 2358754-22-8
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Appearance Solid
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Molecular Weight 434.57
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Formula C27H34N2O3
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Color Off-white to light brown
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SMILES
COC1=C(OC)C=C(C(CCC2=CNC3=C2C=CC=C3)N(CC4CCOCC4)CC5)C5=C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (230.11 mM; Need ultrasonic; 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 (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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 (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
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: ≥ 2.5 mg/mL (5.75 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
In Vivo Dissolution Calculator
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.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocols
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Cytoplasmic-Nuclear Fractionated Protein Extraction
Cytoplasmic-nuclear fractionated protein extraction separates soluble cytoplasmic proteins from nuclear-enriched proteins by mild plasma-membrane permeabilization, differential centrifugation, washing of nuclei, and extraction of nuclear proteins for downstream immunoblotting or related molecular analysis. The readout is the relative abundance of a protein in cytoplasmic and nuclear fractions, commonly assessed by western blotting together with compartment markers such as tubulin or pyruvate kinase for cytoplasm and lamin, nucleoporin, hnRNP, H2AX, or Lamin B for nuclear fractions.
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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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Lysosome and acidic-vesicle live-cell staining
Lysosome and acidic-vesicle live-cell staining detects acidic intracellular compartments by using membrane-permeant acidotropic probes that accumulate in low-pH vesicles, including lysosomes, late endosomes, autolysosomes, and acidic phagosomes. LysoTracker staining is commonly used as an intensity-based readout of acidic lysosomal compartment abundance or enlargement, while acridine orange produces green fluorescence in less concentrated compartments and red fluorescence after concentration-dependent accumulation in acidic vesicular organelles. Loss or reduction of acridine-orange red signal can be used as a readout of lysosomal membrane permeabilization or reduced acidic-vesicle integrity. This protocol is designed for live cultured cells and can be adapted for fluorescence microscopy, high-content imaging, plate-reader readout, or flow cytometry when the selected literature supports the readout. Because these dyes report acidotropic accumulation rather than lysosome identity alone,
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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
Purity & Documentation
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Data Sheet (282 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 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 (stored under nitrogen). 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 |
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| DMSO | 1 mM | 2.3011 mL | 11.5056 mL | 23.0113 mL | 57.5281 mL |
| 5 mM | 0.4602 mL | 2.3011 mL | 4.6023 mL | 11.5056 mL | |
| 10 mM | 0.2301 mL | 1.1506 mL | 2.3011 mL | 5.7528 mL | |
| 15 mM | 0.1534 mL | 0.7670 mL | 1.5341 mL | 3.8352 mL | |
| 20 mM | 0.1151 mL | 0.5753 mL | 1.1506 mL | 2.8764 mL | |
| 25 mM | 0.0920 mL | 0.4602 mL | 0.9205 mL | 2.3011 mL | |
| 30 mM | 0.0767 mL | 0.3835 mL | 0.7670 mL | 1.9176 mL | |
| 40 mM | 0.0575 mL | 0.2876 mL | 0.5753 mL | 1.4382 mL | |
| 50 mM | 0.0460 mL | 0.2301 mL | 0.4602 mL | 1.1506 mL | |
| 60 mM | 0.0384 mL | 0.1918 mL | 0.3835 mL | 0.9588 mL | |
| 80 mM | 0.0288 mL | 0.1438 mL | 0.2876 mL | 0.7191 mL | |
| 100 mM | 0.0230 mL | 0.1151 mL | 0.2301 mL | 0.5753 mL |
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