CYM-5478 (CYM5478) is a novel and potent agonist for S1P2 (Sphingosine 1-phosphate receptor 2, EC50 = 119 nM in a TGFα-shedding assay). CYM 5478 can protect neural-derived cell lines against Cisplatin toxicity.
Physicochemical Properties
| Molecular Formula | C21H19F3N2O2 |
| Molecular Weight | 388.4 |
| Exact Mass | 388.139 |
| Elemental Analysis | C, 64.94; H, 4.93; F, 14.67; N, 7.21; O, 8.24 |
| CAS # | 870762-83-7 |
| PubChem CID | 7802604 |
| Appearance | White to off-white solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 527.1±50.0 °C at 760 mmHg |
| Flash Point | 272.6±30.1 °C |
| Vapour Pressure | 0.0±1.4 mmHg at 25°C |
| Index of Refraction | 1.558 |
| LogP | 3.82 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 28 |
| Complexity | 665 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | FC(C1C([H])=C([H])C(N(C=1[H])C([H])([H])C(C1C([H])=C(C([H])([H])[H])N(C([H])([H])C2C([H])=C([H])C([H])=C([H])C=2[H])C=1C([H])([H])[H])=O)=O)(F)F |
| InChi Key | RGSGTUIDJXHTTO-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H19F3N2O2/c1-14-10-18(15(2)26(14)11-16-6-4-3-5-7-16)19(27)13-25-12-17(21(22,23)24)8-9-20(25)28/h3-10,12H,11,13H2,1-2H3 |
| Chemical Name | 1-[2-(1-Benzyl-2,5-dimethylpyrrol-3-yl)-2-oxoethyl]-5-(trifluoromethyl)pyridin-2-one |
| Synonyms | CYM5478 CYM 5478 CYM-5478 |
| 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 |
| 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 |
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| ln Vitro | In comparison to the other S1P receptor subtypes (EC50 of 1690 nM, 1950 nM, >10 μM, >10 μM for S1P1, S1P3, S1P4, and S1P5, respectively), CYM-5478 activates S1P2 with an EC50 of 119 nM, has less than 25% efficacy, and exhibits ten-fold reduced potency[1]. When serum fasting promotes nutrient-deprivation stress, CYM-5478 (1, 10, 100, 1000, and 10,000 nM) increases C6 cell viability in a dose-dependent manner at concentrations above 100 nM. When 10% fetal bovine serum was present, this effect did not occur[1]. CYM-5478 (10 μM) considerably attenuates the increase of ROS in C6 cells exposed to Cisplatin (20 μM; for 24 hours), and it also induces a statistically significant, 3-fold increase in the EC50 of Cisplatin-mediated decrease [1]. When exposed to Cisplatin toxicity, brain cells are shielded by CYM-5478 (20 μM) but not breast cancer cells (EC50=4.54 μM for C6 glioma cells, 17 μM for GT1-7, 7.44 μM for SK-N-BE2, and 5.54 μM for CLU188)[2]. | |
| ln Vivo | Rats exposed to Cisplatin-mediated ototoxicity (3 mg/kg; ip; once a week for three weeks) are protected against by CYM-5478 (1 mg/kg/day; ip)[2]. When CYM-5478 (20 μM) is administered, neuromast viability loss caused by cisplatin is almost completely prevented. CYM-5478 guards against ototoxicity-related loss of hair cell viability in a zebrafish model[2]. | |
| References |
[1]. Sphingosine 1-phosphate receptor 2 (S1P2) attenuates reactive oxygen species formation and inhibits cell death: implications for otoprotective therapy. Sci Rep. 2016 Apr 15;6:24541. [2]. Sphingosine 1-Phosphate Receptor 2 Induces Otoprotective Responses to Cisplatin Treatment. Cancers (Basel). 2020 Jan 15;12(1):211. |
Solubility Data
| 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 |
| 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 | 2.5747 mL | 12.8733 mL | 25.7467 mL | |
| 5 mM | 0.5149 mL | 2.5747 mL | 5.1493 mL | |
| 10 mM | 0.2575 mL | 1.2873 mL | 2.5747 mL |