Physicochemical Properties
| Molecular Formula | C18H28F3N2O6P |
| Molecular Weight | 456.393696784973 |
| Exact Mass | 456.163 |
| CAS # | 909725-62-8 |
| Related CAS # | W146;909725-61-7 |
| PubChem CID | 6857802 |
| Appearance | White to off-white solid powder |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 23 |
| Complexity | 400 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | P(CCC(C(NC1=CC=CC(=C1)CCCCCC)=O)N)(=O)(O)O.FC(C(=O)O)(F)F |
| InChi Key | JDWCNCPWPLHFEX-XFULWGLBSA-N |
| InChi Code | InChI=1S/C16H27N2O4P.C2HF3O2/c1-2-3-4-5-7-13-8-6-9-14(12-13)18-16(19)15(17)10-11-23(20,21)22;3-2(4,5)1(6)7/h6,8-9,12,15H,2-5,7,10-11,17H2,1H3,(H,18,19)(H2,20,21,22);(H,6,7)/t15-;/m1./s1 |
| Chemical Name | [(3R)-3-amino-4-(3-hexylanilino)-4-oxobutyl]phosphonic acid;2,2,2-trifluoroacetic acid |
| HS Tariff Code | 2934.99.9001 |
| 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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | EC50: 398 nM (S1PR1)[1]. |
| ln Vitro | W146 is an antagonist of S1PR1 with a Ki of roughly 70–80 nM[1]. The W146 pretreatment markedly raised the amounts of activated cleaved caspase-3. The S1P-induced decrease in EPC apoptosis totally vanished following W146 therapy [2]. |
| ln Vivo | Pretreatment with W146 (5 mg/kg, ip) prior to AMD3100 administration resulted in an approximately 8-fold increase in KSL-HSPC mobilization as compared to mice treated with AMD3100 alone, as shown by the CFU-G/M colony formation assay [3]. The particular augmentation of KSL-HSPC mobilization by W146 was mediated, since pretreatment of mice with W140 did not affect the activation of AMD3100-stimulated KSL-HSPC. Mice's basal WBC counts remain unchanged after injections of W146, W140, JTE013 or Cay10444 [3]. |
| Cell Assay |
Apoptosis Analysis[2] Cell Types: Endothelial progenitor cells (EPCs). Tested Concentrations: 10 μM. Incubation Duration: 30 min before the addition of S1P. Experimental Results: Increases activated cleaved caspase-3 levels. |
| Animal Protocol |
Animal/Disease Models: Mice (4-6weeks old)[3] . Doses: 5 mg/kg. Route of Administration: IP, 1 hour prior to AMD3100 (ADM) administration. Experimental Results: Dramatically increased in KSL-HSPC mobilization compared to that in mice pretreated with dextran followed by AMD3100 administration. |
| References |
[1]. Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo. Nat Chem Biol. 2006 Aug;2(8):434-41. Epub 2006 Jul 9. [2]. 3-amino-4-(3-hexylphenylamino)-4-oxobutyl phosphonic acid (W146), a Selective Antagonist of Sphingosine-1-phospahte Receptor Subtype 1, Enhances AMD3100-stimulated Mobilization of Hematopoietic Stem Progenitor Cells in Animals. J Biochem Pharmacol Res. 2013 Dec; 1(4): 197–203. [3]. Sphingosine-1-phosphate promotes the proliferation and attenuates apoptosis of Endothelial progenitor cells via S1PR1/S1PR3/PI3K/Akt pathway. Cell Biol Int. 2018 May 23. |
| Additional Infomation | [(3R)-3-aMino-4-[(3-hexylphenyl)aMino]-4-oxobutyl]-phosphonic acid is an amino acid amide. |
Solubility Data
| Solubility (In Vitro) | DMSO : 22.73 mg/mL (49.80 mM) |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1911 mL | 10.9555 mL | 21.9111 mL | |
| 5 mM | 0.4382 mL | 2.1911 mL | 4.3822 mL | |
| 10 mM | 0.2191 mL | 1.0956 mL | 2.1911 mL |