| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
ARN14988 specifically targets acid ceramidase (ACDase), a key enzyme in sphingolipid metabolism. It acts as a potent inhibitor of the human acid ceramidase enzyme with an IC50 of 12.8 nM, blocking the hydrolysis of ceramide into sphingosine and free fatty acid.
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| ln Vitro |
ARN14988 exhibits potent in vitro activity by inhibiting acid ceramidase. It increases the levels of C16 dihydro ceramide and C16 ceramide in various melanoma cell lines, including A375, G361, M14, MeWo, MNT-1, and SK-MEL-28. This elevation in ceramide levels contributes to its antiproliferative and pro-apoptotic effects in cancer cells.
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| ln Vivo |
In vivo, ARN14988 has been shown to normalize ceramide levels and sensitize proliferative melanoma cells to the cytotoxic actions of various antitumoral agents. While detailed animal efficacy data is limited, its mechanism of action suggests it could enhance the efficacy of other chemotherapeutic agents by restoring ceramide-mediated apoptotic signaling.
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| Enzyme Assay |
The enzyme inhibition assay for ARN14988 typically involves measuring acid ceramidase activity in cell lysates or using recombinant human enzyme. The reaction is initiated by adding a fluorescent substrate (e.g., RBM14C12) to the enzyme in the presence of varying concentrations of ARN14988 (0-1000 nM). After incubation at 37degC for 1-2 hours, the reaction is terminated, and fluorescence is measured to calculate IC50.
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| Cell Assay |
For cell-based assays, melanoma cells (e.g., A375, G361) are seeded in 96-well plates (5000-10000 cells/well) and treated with ARN14988 at concentrations ranging from 0.1 uM to 100 uM for 24-72 hours. Cells are then lysed, and ceramide levels are quantified by LC-MS/MS. Cell viability is assessed using MTT, CellTiter-Glo, or Annexin V staining for apoptosis.
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| Animal Protocol |
In vivo protocols for ARN14988 typically involve subcutaneous implantation of melanoma cells (e.g., A375) into immunocompromised mice. Once tumors reach ~100-200 mm3, ARN14988 is administered orally or intraperitoneally (5-25 mg/kg) daily for 2-4 weeks. Tumor volume, body weight, and tissue ceramide levels are monitored. Combination studies with other agents are common.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for ARN14988 is limited. Based on its chemical properties, it is expected to have moderate oral bioavailability. As a potent enzyme inhibitor, it likely distributes into tissues where acid ceramidase is expressed. Researchers should conduct their own PK studies for specific experimental contexts.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for ARN14988 is not publicly available. As an acid ceramidase inhibitor, its toxicity profile is expected to be related to its mechanism of action. Researchers should refer to safety data sheets and handle the compound with appropriate precautions for potent biochemical agents.
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| References |
[1]. Realini N, et al. Acid Ceramidase in Melanoma: EXPRESSION, LOCALIZATION, AND EFFECTS OF PHARMACOLOGICAL INHIBITION. J Biol Chem. 2016 Jan 29;291(5):2422-34.
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| Additional Infomation |
ARN14988 is a research-use compound for biochemical and pharmacological studies. Its mechanism of action involves inhibiting acid ceramidase, thereby restoring pro-apoptotic ceramide levels. This compound has been explored primarily for its potential in melanoma therapy, either as a monotherapy or in combination with other cytotoxic agents to overcome chemoresistance.
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| Molecular Formula |
C16H24CLN3O5
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|---|---|
| Molecular Weight |
373.83
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| Exact Mass |
373.14
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| CAS # |
1502027-70-4
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| PubChem CID |
72548973
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.542
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| LogP |
2.38
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
25
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| Complexity |
562
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=O)N(C(OCC(C)C)=O)C(=O)C(Cl)=CN1C(NCCCCCC)=O
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| InChi Key |
PBVLSEVDIRSYGE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H24ClN3O5/c1-4-5-6-7-8-18-14(22)19-9-12(17)13(21)20(15(19)23)16(24)25-10-11(2)3/h9,11H,4-8,10H2,1-3H3,(H,18,22)
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| Chemical Name |
2-methylpropyl 5-chloro-3-(hexylcarbamoyl)-2,6-dioxopyrimidine-1-carboxylate
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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 | 2.6750 mL | 13.3751 mL | 26.7501 mL | |
| 5 mM | 0.5350 mL | 2.6750 mL | 5.3500 mL | |
| 10 mM | 0.2675 mL | 1.3375 mL | 2.6750 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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