| 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 |
SMS2 (sphingomyelin synthase 2). SMS2-IN-2 is a potent, selective inhibitor of SMS2 with 560-fold selectivity over SMS1 (100 nM vs 56 microM). SMS2 catalyzes the synthesis of sphingomyelin from ceramide and phosphatidylcholine. By inhibiting SMS2, the compound modulates sphingolipid metabolism, reducing sphingomyelin levels and potentially increasing ceramide.
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| ln Vitro |
SMS2-IN-2 inhibits SMS2 with an IC₅0 of 100 nM and SMS1 with an IC₅0 of 56 microM. The compound shows >560-fold selectivity for SMS2 over SMS1. It exhibits anti-chronic inflammatory activity. The compound is orally active, making it suitable for in vivo studies of sphingolipid metabolism and inflammation.
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| ln Vivo |
In mice with db/db backgrounds, SMS2-IN-2 (compound 15w; 20, 50 mg/kg/day, orally for 6 weeks) decreases chronic inflammation [1].
In vivo, SMS2-IN-2 is expected to demonstrate anti-inflammatory activity in models of chronic inflammation. As an orally active compound, it is suitable for oral administration in preclinical studies. Efficacy would be assessed in models of atherosclerosis, metabolic syndrome, or inflammatory diseases where sphingomyelin metabolism plays a role. |
| Enzyme Assay |
SMS2 enzymatic activity is measured using a radiometric or fluorescence-based assay. SMS2 converts ceramide and phosphatidylcholine to sphingomyelin. Microsomal membranes containing SMS2 are incubated with radiolabeled ceramide or fluorescent substrates and serial dilutions of test compound. Product formation is quantified, and IC₅0 values are calculated from dose-response curves.
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| Cell Assay |
Cells (e.g., macrophages, hepatocytes, or adipocytes) are treated with SMS2-IN-2 at various concentrations. Sphingomyelin and ceramide levels are measured by LC-MS/MS. Inflammatory cytokine production (TNF-alpha, IL-6, IL-1beta) is assessed by ELISA. Cell viability is evaluated using MTT or CellTiter-Glo assays.
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| Animal Protocol |
Animal/Disease Models: Type 2 Diabetes Mellitus (T2DM) db/db mouse model (4 to 5 weeks) [1]
Doses: 20, 50 mg/kg/day Route of Administration: Oral daily for 6 weeks Experimental Results: IL-6 Dramatically lower and insulin levels. Mouse models of chronic inflammation (e.g., LPS-induced inflammation, atherosclerosis models, or high-fat diet-induced metabolic syndrome) are administered SMS2-IN-2 orally. Inflammatory markers in serum and tissues are measured. Sphingolipid levels in plasma and tissues are quantified by LC-MS/MS. Efficacy is determined by reduction in inflammatory markers and improvement of disease phenotypes. |
| ADME/Pharmacokinetics |
SMS2-IN-2 has a molecular weight of 369.78 g/mol and formula C1₉H13ClFN3O2. As an orally active compound, it is expected to have favorable oral bioavailability. Standard PK parameters would be determined in rodent studies following PO and IV administration. The compound is formulated in suitable vehicles for oral gavage.
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| Toxicity/Toxicokinetics |
Toxicology data for SMS2-IN-2 are not publicly available. Standard preclinical safety assessment would include cytotoxicity assays, hERG testing, and repeat-dose toxicology studies in rodents. Given the role of sphingolipids in normal cellular function, potential on-target and off-target effects would be evaluated.
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| References | |
| Additional Infomation |
SMS2-IN-2 is a research compound for studying sphingolipid metabolism and inflammation. It is not clinically approved. The compound's high selectivity for SMS2 over SMS1 (>560-fold) makes it a valuable tool for dissecting the distinct roles of SMS1 and SMS2 in sphingolipid metabolism and disease. It is useful for investigating SMS2 as a therapeutic target for inflammatory and metabolic diseases.
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| Molecular Formula |
C19H13CLFN3O2
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|---|---|
| Molecular Weight |
369.776826620102
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| Exact Mass |
369.068
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| CAS # |
2241838-28-6
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| PubChem CID |
134813905
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| Appearance |
White to off-white solid powder
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| LogP |
4.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
461
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC(=CC=1COC1=CC=CC2=C1C(=NO2)NC1C=NC=CC=1)F
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| InChi Key |
VZWFUUUUCXTDJT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H13ClFN3O2/c20-15-7-6-13(21)9-12(15)11-25-16-4-1-5-17-18(16)19(24-26-17)23-14-3-2-8-22-10-14/h1-10H,11H2,(H,23,24)
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| Chemical Name |
4-[(2-chloro-5-fluorophenyl)methoxy]-N-pyridin-3-yl-1,2-benzoxazol-3-amine
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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 : ~125 mg/mL (~338.04 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.62 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 (5.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7043 mL | 13.5216 mL | 27.0431 mL | |
| 5 mM | 0.5409 mL | 2.7043 mL | 5.4086 mL | |
| 10 mM | 0.2704 mL | 1.3522 mL | 2.7043 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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