| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg | |||
| Other Sizes |
| Targets |
Acid ceramidase (ACDase) and lysosomal acid sphingomyelinase (ASMase). LCL521 is an inhibitor of both of these key enzymes in sphingolipid metabolism. By inhibiting ACDase and ASMase, it blocks sphingolipid catabolism, leading to intracellular ceramide accumulation and altered sphingolipid signaling.
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| ln Vitro |
LCL521 (1 µM) is a powerful inhibitor of cellular ACDase activity, but 10 µM LCL521 has an extra, weakened action on the alpha form of this enzyme. LCL521 (10 µM) causes a time-dependent (1 hour and 5 hour) decrease of α-ACDase forms in MCF7 cells [1].
LCL521 (1 µM) is a potent inhibitor of cellular ACDase activity. In MCF7 cells, 10 µM LCL521 decreases α-ACDase levels within 1-5 hours, enabling selective modulation of ceramide turnover. It also inhibits lysosomal acid sphingomyelinase (ASMase). At 10 µM, LCL521 significantly reduces sphingosine levels while increasing ceramide. It affects the processing and regeneration of ACDase protein. |
| ln Vivo |
In vivo, LCL521 has been shown to significantly decrease myeloid-derived suppressor cell (MDSC) accumulation. It effectively suppresses MDSCs by disrupting autophagy and inducing ER stress, leading to cell death, which holds potential in immunotherapy by enhancing CTL-based cancer treatments. LCL521 targets lysosomes and increases total cellular C16 ceramide levels.
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| Enzyme Assay |
In vitro assays for LCL521 typically involve measuring its inhibitory activity against acid ceramidase (ACDase) and acid sphingomyelinase (ASMase). The compound is incubated with the enzyme and a fluorogenic or radiolabeled substrate. The rate of substrate hydrolysis is measured, and IC50 values are determined. The compound's effect on ceramide and sphingosine levels in cell lysates can also be assessed by LC-MS/MS.
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| Cell Assay |
In vitro cell-based assays for LCL521 are performed to study its effects on sphingolipid metabolism and cell viability. Cells (e.g., MCF7) are treated with the compound, and the levels of ceramide, sphingosine, and other sphingolipids are measured by LC-MS/MS. The compound's effect on cell viability, apoptosis, and autophagy can also be assessed. It is used to study the role of ceramide in cell death and stress responses.
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| Animal Protocol |
In vivo animal studies for LCL521 are conducted to evaluate its effects on MDSC accumulation and tumor growth. The compound is administered to tumor-bearing mice, and the percentage of MDSCs in the spleen and tumor is measured. Its effects on autophagy, ER stress, and immune cell function can also be assessed.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data are available for LCL521 in the provided sources. As a cell-permeable inhibitor, it is expected to have reasonable cell permeability. The compound should be stored as powder at -20°C. For in vivo administration, it would need to be formulated in a suitable vehicle.
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| Toxicity/Toxicokinetics |
No specific toxicity data are documented for LCL521 in the provided sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. Standard laboratory safety practices should be followed when handling this compound.
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| References | |
| Additional Infomation |
LCL521 is a cell-permeable inhibitor of acid ceramidase (ACDase) and acid sphingomyelinase (ASMase). It is also known as 1,3DMG-B13. Its IUPAC name is (1R,2R)-1-(4-nitrophenyl)-2-tetradecanamidopropane-1,3-diyl bis(2-(dimethylamino)acetate). It is a lysosomotropic inhibitor with anticancer activity and is used in research on ceramide signaling and immunotherapy.
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| Molecular Formula |
C31H52N4O7
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|---|---|
| Molecular Weight |
592.767189025879
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| Exact Mass |
592.383
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| CAS # |
1226851-11-1
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| Related CAS # |
LCL521 dihydrochloride;1226759-47-2
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| PubChem CID |
46200045
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| Appearance |
Colorless to light yellow ointment
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| LogP |
7.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
42
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| Complexity |
780
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CCCCCCCCCCCCCC(=O)N[C@H](COC(=O)CN(C)C)[C@@H](C1=CC=C(C=C1)[N+](=O)[O-])OC(=O)CN(C)C
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| InChi Key |
ANWWJORIPQKJFW-DLFZDVPBSA-N
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| InChi Code |
InChI=1S/C31H52N4O7/c1-6-7-8-9-10-11-12-13-14-15-16-17-28(36)32-27(24-41-29(37)22-33(2)3)31(42-30(38)23-34(4)5)25-18-20-26(21-19-25)35(39)40/h18-21,27,31H,6-17,22-24H2,1-5H3,(H,32,36)/t27-,31-/m1/s1
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| Chemical Name |
[(2R,3R)-3-[2-(dimethylamino)acetyl]oxy-3-(4-nitrophenyl)-2-(tetradecanoylamino)propyl] 2-(dimethylamino)acetate
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| Synonyms |
LCL 521 LCL-521 LCL521
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6870 mL | 8.4350 mL | 16.8699 mL | |
| 5 mM | 0.3374 mL | 1.6870 mL | 3.3740 mL | |
| 10 mM | 0.1687 mL | 0.8435 mL | 1.6870 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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