| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
Acid ceramidase (ACDase) and lysosomal acid sphingomyelinase (ASMase). LCL521 dihydrochloride 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 (10μM) causes a time-dependent (1 hour and 5 hour) decrease of α-ACDase forms in MCF7 cells [1].
As the dihydrochloride salt of LCL521, this compound shares the same biological activity as the free base. It is a potent inhibitor of acid ceramidase (ACDase) and also inhibits lysosomal acid sphingomyelinase (ASMase). Its effects on sphingolipid metabolism, including ceramide accumulation, are expected to be identical to LCL521. |
| ln Vivo |
In vivo, LCL521 dihydrochloride is expected to have similar effects to the free base, including the ability to decrease myeloid-derived suppressor cell (MDSC) accumulation. It targets lysosomes and increases total cellular C16 ceramide levels. The dihydrochloride salt form may offer advantages in formulation for in vivo administration due to its improved aqueous solubility.
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| Enzyme Assay |
In vitro assays for LCL521 dihydrochloride are the same as those for the free base. They involve measuring its inhibitory activity against acid ceramidase (ACDase) and acid sphingomyelinase (ASMase) using fluorogenic or radiolabeled substrates. IC50 values are determined from concentration-response curves. The compound's effect on ceramide and sphingosine levels in cell lysates can be assessed by LC-MS/MS.
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| Cell Assay |
In vitro cell-based assays for LCL521 dihydrochloride are performed using cell lines such as MCF7. Cells are treated with the compound, and the levels of ceramide, sphingosine, and other sphingolipids are measured. The compound's effect on cell viability, apoptosis, and autophagy can also be assessed. The dihydrochloride salt may be more readily soluble in cell culture media.
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| Animal Protocol |
In vivo animal studies for LCL521 dihydrochloride would be similar to those for the free base. The compound could be administered to tumor-bearing mice to study its effects on MDSC accumulation and tumor growth. The dihydrochloride salt form may offer advantages in formulation for in vivo administration due to its improved aqueous solubility.
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| ADME/Pharmacokinetics |
LCL521 dihydrochloride has a molecular weight of 665.69 and a molecular formula of C31H54Cl2N4O7. The dihydrochloride salt form is used to improve aqueous solubility and stability. It should be stored as powder at -20°C. It is soluble in aqueous solutions.
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| Toxicity/Toxicokinetics |
No specific toxicity data are documented for LCL521 dihydrochloride 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 dihydrochloride is the dihydrochloride salt of LCL521, also known as 1,3DMG-B13 dihydrochloride. It is a novel and potent acid ceramidase (ACDase) inhibitor that also inhibits lysosomal acid sphingomyelinase (ASMase). Its IUPAC name is (1R,2R)-1-(4-nitrophenyl)-2-tetradecanamidopropane-1,3-diyl bis(2-(dimethylamino)acetate) dihydrochloride.
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| Molecular Formula |
C31H54CL2N4O7
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|---|---|
| Molecular Weight |
665.689067363739
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| Exact Mass |
664.336
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| CAS # |
1226759-47-2
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| Related CAS # |
LCL521;1226851-11-1
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| PubChem CID |
132585217
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
44
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| Complexity |
780
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| Defined Atom Stereocenter Count |
2
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| SMILES |
Cl.Cl.O(C(CN(C)C)=O)[C@H](C1C=CC(=CC=1)[N+](=O)[O-])[C@@H](COC(CN(C)C)=O)NC(CCCCCCCCCCCCC)=O
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| InChi Key |
RGUSRMLMLNVDSF-QJCVVZHISA-N
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| InChi Code |
InChI=1S/C31H52N4O7.2ClH/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)2*1H/t27-,31-/m1../s1
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| Chemical Name |
(1R,2R)-1-(4-nitrophenyl)-2-tetradecanamidopropane-1,3-diyl bis(2-(dimethylamino)acetate) dihydrochloride
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| Synonyms |
LCL521 dihydrochloride LCL-521 dihydrochloride LCL 521 dihydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O : ~100 mg/mL (~150.22 mM)
DMSO : ~20.83 mg/mL (~31.29 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.12 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.12 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.12 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 50 mg/mL (75.11 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5022 mL | 7.5110 mL | 15.0220 mL | |
| 5 mM | 0.3004 mL | 1.5022 mL | 3.0044 mL | |
| 10 mM | 0.1502 mL | 0.7511 mL | 1.5022 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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