| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
SLF-1081851 TFA targets Spns2 (Spinster Homolog 2), a transporter that exports sphingosine-1-phosphate (S1P) from cells. It inhibits S1P release (IC50 = 1.93 µM), thereby modulating S1P gradients that regulate lymphocyte trafficking and immune responses. It shows at least 15-fold selectivity over SphK1 and SphK2.
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|---|---|
| ln Vitro |
Sphingosine-1-phosphate (S1P) is a pleiotropic signaling molecule, and Spns2 functions to maintain lymphatic S1P [1]. SLF1081851 (TFA) (Compound 16d) (0-5 μM; 18-20 hours) inhibits S1P release in Hela cells with an IC50 value of 1.93 μM [1]. SLF1081851 (TFA) (0-30 μM; 20 min) inhibits mSphK1 (recombinant mouse SphK) (10 μM) and mSphK2 (5 μM) in a dose-dependent manner and shows at least 15-fold selectivity (SphK1 IC50≥30 μM); SphK2 IC50≈30 μM) [1].
In vitro, SLF-1081851 TFA inhibits S1P release in HeLa cells with an IC50 of 1.93 µM. It also inhibits mSphK1 and mSphK2 in a dose-dependent manner with at least 15-fold selectivity for Spns2. |
| ln Vivo |
The genetic phenotype of Spns2-null mice is recapitulated by SLF1081851 (TFA) (20 mg/kg; i.p., 4 hours post-dose), which also significantly inhibits circulating lymphocytes and plasma S1P [1].
In vivo, SLF-1081851 TFA (20 mg/kg, i.p.) significantly inhibits circulating lymphocytes and plasma S1P in C57BL/6 mice. The genetic phenotype of Spns2-null mice is recapitulated by the compound. |
| Enzyme Assay |
For non-cell assays, SLF-1081851 TFA is tested for Spns2 inhibition using membrane vesicles expressing Spns2 or cell-based S1P release assays. S1P levels are measured by LC-MS/MS.
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| Cell Assay |
In cell assays, HeLa cells are treated with SLF-1081851 TFA (0-5 µM) for 18-20 hours, and S1P release is measured by LC-MS/MS. SphK1 and SphK2 activities are measured using recombinant enzymes.
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| Animal Protocol |
Animal/Disease Models: C57BL/6 mice [1]
Doses: 20 mg/kg Route of Administration: intraperitoneal (ip) injection; blood draw results 4 hrs (hrs (hours)) after taking the drug: circulating lymphocyte count and plasma S1P concentration were Dramatically diminished. Animal/Disease Models: SpragueDawley mice (4 weeks old) [1] Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection; single dose; measurement results at 0, 0.5, 1, 2, 4, 6 and 24 hrs (hrs (hours)) after administration Experimental Results: The maximum concentration of 5 μM is reached in the blood after 2 hrs (hrs (hours)), and the drug level is maintained at ≥ 2 μM for at least 24 hrs (hrs (hours)), proving that the lifespan of rats with half concentration exceeds 8 hrs (hrs (hours)). The appearance of SPNS2-IN-1 in the circulation was associated with a maximal reduction in lymphocyte counts at 4 h (25% reduction compared to time = 0). In vivo animal protocols use C57BL/6 mice. SLF-1081851 TFA is dissolved in DMSO/PEG/saline and administered intraperitoneally at 20 mg/kg. Circulating lymphocyte counts and plasma S1P concentrations are measured 4 hours post-dose. |
| References |
| Molecular Formula |
C23H34F3N3O3
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|---|---|
| Molecular Weight |
457.529576778412
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| Exact Mass |
457.255
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| CAS # |
2763730-98-7
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| Related CAS # |
SLF1081851;2763730-97-6
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| PubChem CID |
165412597
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| Appearance |
Typically exists as solid at room temperature
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| tPSA |
102
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
32
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| Complexity |
402
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCCCCCCCCCC1=CC=C(C=C1)C2=NOC(=N2)CCCN.C(=O)(C(F)(F)F)O
|
| InChi Key |
KSPAYUOYCICAHW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H33N3O.C2HF3O2/c1-2-3-4-5-6-7-8-9-11-18-13-15-19(16-14-18)21-23-20(25-24-21)12-10-17-22;3-2(4,5)1(6)7/h13-16H,2-12,17,22H2,1H3;(H,6,7)
|
| Chemical Name |
3-[3-(4-decylphenyl)-1,2,4-oxadiazol-5-yl]propan-1-amine;2,2,2-trifluoroacetic acid
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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 | 2.1856 mL | 10.9282 mL | 21.8565 mL | |
| 5 mM | 0.4371 mL | 2.1856 mL | 4.3713 mL | |
| 10 mM | 0.2186 mL | 1.0928 mL | 2.1856 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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