| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 0.54±0.06 μM (hCerS1), 0.46±0.08 μM (mCerS1), 28.6±0.15 μM (hCerS2), 18.5±0.12 μM (mCerS2), 17.2±0.09 μM (hCerS4), 7.2±0.10 μM (mCerS5), 11.4±0.17 μM (hCerS6)[1]
Ceramide synthase 1 (CerS1) |
|---|---|
| ln Vitro |
The first isoform-specific inhibitor of ceramide synthase is P053. P053 has a nanomolar efficacy to inhibit CerS1. The CerS isoforms hCerS1, mCerS1, hCerS2, mCerS4, mCerS5, and hCerS6 that are different in humans (h) or mice (m) are inhibited by P053 with IC50 values of 0.54 ±0.06, 0.46±0.08, 28.6±0.15, 18.5±0.12, 17.2±0.09, 7.2±0.10, and 11.4±0.17 μM, respectively[1].
P053 inhibits CerS1 with an IC50 of 0.5 uM (human) and 0.46 uM (mouse). It exhibits high selectivity for CerS1 over CerS2, CerS4, CerS5, and CerS6, with IC50 values of 28.6, 17.2, 7.2, and 11.4 uM, respectively. P053 inhibits different human and murine CerS isoforms with varying potencies. It functions as an endogenous inhibitor of mitochondrial fatty acid oxidation in muscle cells. |
| ln Vivo |
P053 (5 mg/kg; given orally once daily for seven days to male C57BL6/J mice) lowers the levels of C18 ceramide in skeletal muscle (SkM)[1]. Giving mice on a high-fat diet (HFD) on a daily basis improves the amount of fatty acid oxidation in their skeletal muscle and prevents the growth of muscle triglycerides and obesity, but it has no protective effect against insulin resistance brought on by HFDs[1].
Daily oral administration of P053 (5 mg/kg) to male C57BL6/J mice for one week significantly reduces C18 ceramide levels in skeletal muscle (SkM). In mice fed a high-fat diet (HFD), daily P053 administration increases fatty acid oxidation in skeletal muscle and impedes increases in muscle triglycerides and adiposity. However, it does not protect against HFD-induced insulin resistance. Pharmacological inhibition of CerS1 with P053 delays wound healing in mice, validating the sphingosine-CerS1-ceramide axis in wound healing. |
| Enzyme Assay |
For enzyme inhibition assays, recombinant human or mouse CerS1 is expressed in insect cells or HEK293 cells and microsomal fractions are prepared. The assay uses C18-sphingosine as substrate and [14C]-palmitoyl-CoA or [3H]-acetyl-CoA as cofactor. The reaction is incubated at 37degC for 2 hours, stopped by organic extraction, and products separated by TLC or HPLC with radiometric detection. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cells (e.g., HEK293T, HeLa, or primary myotubes) are cultured in DMEM with 10% FBS. Cells are treated with P053 (0.1-10 uM) for 24-48 hours. Ceramide species (C14-C24) are quantified by LC-MS/MS lipidomics after extraction. Fatty acid oxidation is measured by the conversion of [14C]-palmitate to 14CO2 or acid-soluble metabolites in intact cells. Cellular triglyceride content is measured using colorimetric kits. Cell viability is assessed by MTT assay.
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| Animal Protocol |
Animal/Disease Models: Male C57BL6/J mice[1]
Doses: 5 mg/kg Route of Administration: Oral gavage; daily Experimental Results: decreased C18 ceramide levels in SkM by 31%, whereas 1 mg/kg/day had no effect. Male C57BL6/J mice are fed a high-fat diet (HFD; 60% kcal from fat) for 8-12 weeks to induce obesity and insulin resistance. P053 is administered orally (gavage) at doses of 1-10 mg/kg daily for 1-8 weeks. Endpoints include tissue ceramide levels (LC-MS/MS), skeletal muscle fatty acid oxidation (ex vivo using 14C-palmitate), plasma triglycerides, insulin sensitivity (HOMA-IR or hyperinsulinemic-euglycemic clamp), body weight, and wound healing assays. |
| ADME/Pharmacokinetics |
Following a single 5 mg/kg oral dose in mice, P053 achieves measurable plasma concentrations, with studies reporting plasma concentration-time profiles. The compound shows good oral bioavailability. It is distributed to tissues including skeletal muscle where it exerts its CerS1 inhibitory effects. Detailed pharmacokinetic parameters (half-life, Cmax, AUC, clearance) are available in the literature but vary depending on formulation and dose.
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| Toxicity/Toxicokinetics |
No specific toxicity data reported for P053; however, as a CerS1 inhibitor, it may influence various physiological processes given the role of ceramides in cell signaling, apoptosis, and metabolism. Short-term administration (up to 8 weeks) in mice at 5 mg/kg daily is generally well tolerated without overt signs of toxicity. Long-term safety studies are not publicly available.
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| References | |
| Additional Infomation |
P053 is a first-in-class selective CerS1 inhibitor that modulates ceramide metabolism and fatty acid oxidation. It is a valuable research tool for studying sphingolipid biology, insulin resistance, obesity, and wound healing. It is not approved for clinical use. The compound has the molecular formula C18H21Cl2NO2 and molecular weight 354.27. It is supplied as a white to off-white solid powder. References include publications on its role in fat metabolism (2018) and wound healing (2025).
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| Molecular Formula |
C18H21CL2NO2
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|---|---|
| Molecular Weight |
354.270843267441
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| Exact Mass |
353.094
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| CAS # |
2748196-63-4
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| PubChem CID |
137700518
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| Appearance |
White to off-white solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
23
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| Complexity |
350
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(C1C=CC(=C(C=1)Cl)Cl)OC1C=CC(=CC=1)CC[C@@](N)(C)CO
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| InChi Key |
ZQQHXJCIFGMUPY-SFHVURJKSA-N
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| InChi Code |
InChI=1S/C18H21Cl2NO2/c1-18(21,12-22)9-8-13-2-5-15(6-3-13)23-11-14-4-7-16(19)17(20)10-14/h2-7,10,22H,8-9,11-12,21H2,1H3/t18-/m0/s1
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| Chemical Name |
(2S)-2-amino-4-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-methylbutan-1-ol
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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) |
DMSO: 100 mg/mL (282.27 mM)
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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 | 2.8227 mL | 14.1135 mL | 28.2271 mL | |
| 5 mM | 0.5645 mL | 2.8227 mL | 5.6454 mL | |
| 10 mM | 0.2823 mL | 1.4114 mL | 2.8227 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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