 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C21H16CLN3O5 |
| Molecular Weight | 425.821844100952 |
| Exact Mass | 425.077 |
| CAS # | 1315311-14-8 |
| PubChem CID | 53312127 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 4.8 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 30 |
| Complexity | 587 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C(O)(=O)COC1=C(C)C=C(C2=NC3=CN=C(OC4=CC=CC(Cl)=C4)N=C3O2)C=C1C |
| InChi Key | WRBZNIUFAKIIQG-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H16ClN3O5/c1-11-6-13(7-12(2)18(11)28-10-17(26)27)19-24-16-9-23-21(25-20(16)30-19)29-15-5-3-4-14(22)8-15/h3-9H,10H2,1-2H3,(H,26,27) |
| Chemical Name | 2-[4-[5-(3-chlorophenoxy)-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy]acetic 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 | S1PR1 12.6-493 nM (EC50) |
| ln Vitro | In HUVECs, SAR247799 (0, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10 μM; 10 min) phosphorylates extracellular-regulated kinase-1/2 (Erk1/2) and protein kinase B (Akt) in a concentration-dependent manner[1]. In HUVECs, SAR247799 (0-10 μM, 8 min) causes an impedance shift in a dose-dependent way[1]. Ca2+ flow test results in no desensitization in S1P1 Chinese hamster ovary (CHO) cells when exposed to SAR247799 (1 μM, 1st)[1]. |
| ln Vivo | The severity of acute kidney injury caused by ischemia/reperfusion (I/R) is dose-dependently reduced by SAR247799 (1 and 3 mg/kg; po; 1 h before renal occlusion)[1]. In pig models of coronary endothelial dysfunction, SAR247799 (0.3, 1, 3 mg/kg; iv) dose-dependently enhances the coronary conductance ratio[1]. Pigs' exposure (Cmax and AUC) to SAR247799 (30-min intravenous treatment; 8–10 week old farm pigs) rises with dose. Pharmacokinetic parameters[1]: Dose (mg/kg) N Cmax (g/mL) Tmax (h) Tlast (h) AUC0-last (gh/mL) Cl (L/h/kg) Vss (L/kg) T1/2z (h) 1 4 2.08 (8) 0.5 [0.5] [8-48] 11.8 (46) 0.113 (75) 0.516 (11) 5.62 (57) 3 7 8.10 (12) 0.5 [0.5] [24 -72] 42.2 (23) 0.0754 (30) 0.446 (16) 6.21 (28) 10 3 36.7 (5) 0.5 [0.5-0.75] 72 294 (13) 0.0343 (13) 0.338 (7) 7.73 (8) 30 6 112 (27) 0.5 [0.5-1.0] [48-72] 908 (16) 0.0338 (18) 0.294 (11) 7.35 (11) Mean values with (CV%) except Tmax, which is expressed as median value with [range]. Cmax stands for maximum concentration. Tmax, or the time at which concentration reaches its maximum. Tlast is the sampled last time point. Area under the curve from 0 to the last time point is called AUC0-last. Cl, clearing. Vss stands for volume in a steady state or distribution volume. Elimination half-life, T1/2z. N is the total number of creatures. |
| Animal Protocol |
Animal/Disease Models: Acute kidney injury rats (12 to 15weeks old Fischer rats)[1] Doses: 1 and 3 mg /kg Route of Administration: Po; administered 1 hour before renal occlusion. Experimental Results: Inhibited the increase in serum creatinine (89 and 96% at 1 and 3 mg/kg) and urea (61 and 85% at 1 and 3 mg/kg). Protected renal proximal tubules against necrosis and blunted the development of interstitial hemorrhage. Animal/Disease Models: Acute kidney injury rats (8- to 12weeks old Fischer rats)[1] Doses: 3 mg/kg Route of Administration: Po; twice a day for 7 days and twice a day for 7 day Experimental Results: demonstrated a dosedependent trend for reducing macrophage. |
| References |
[1]. A G protein-biased S1P1 agonist, SAR247799, protects endothelial cells without affecting lymphocyte numbers. Sci Signal. 2020 Jun 2;13(634):eaax8050. [2]. A G-protein-biased S1P1 agonist, SAR247799, improved LVH and diastolic function in a rat model of metabolic syndrome. PLoS One. 2022 Jan 14;17(1):e0257929. [3]. Endothelial-protective effects of a G-protein-biased sphingosine-1 phosphate receptor-1 agonist, SAR247799, in type-2 diabetes rats and a randomized placebo-controlled patient trial. Br J Clin Pharmacol. 2021 May;87(5):2303-2320. [4]. First-in-human study of the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple oral doses of SAR247799, a selective G-protein-biased sphingosine-1 phosphate receptor-1 agonist for endothelial protection. |
Solubility Data
| Solubility (In Vitro) | DMSO: 33.33 mg/mL (78.27 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 | 2.3484 mL | 11.7421 mL | 23.4841 mL | |
| 5 mM | 0.4697 mL | 2.3484 mL | 4.6968 mL | |
| 10 mM | 0.2348 mL | 1.1742 mL | 2.3484 mL |