Cenerimod (ACT-334441) is a potent and orally bioavailable immunomodulator, which exhibited an EC50 of 2.7 nM. Cenerimod is an agonist for the G protein-coupled receptor S1 P1/EDG1, and it reduces the amount of circulating and infiltrating T- and B-lymphocytes without impairing their maturation, memory, or expansion. This results in a potent and prolonged immunomodulatory effect. Cenerimod may be helpful in the treatment or prevention of illnesses linked to immune system activation.
Physicochemical Properties
| Molecular Formula | C25H31N3O5 |
| Molecular Weight | 453.54 |
| Exact Mass | 453.226 |
| Elemental Analysis | C, 66.21; H, 6.89; N, 9.27; O, 17.64 |
| CAS # | 1262414-04-9 |
| Related CAS # | 1262414-04-9 |
| PubChem CID | 49871973 |
| Appearance | White to yellow solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 670.7±65.0 °C at 760 mmHg |
| Flash Point | 359.4±34.3 °C |
| Vapour Pressure | 0.0±2.2 mmHg at 25°C |
| Index of Refraction | 1.578 |
| LogP | 5.92 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 33 |
| Complexity | 592 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | OC[C@H](O)COC1=C(C)C=C(C2=NOC(C3=CC(C4CCCC4)=NC(OC)=C3)=N2)C=C1CC |
| InChi Key | KJKKMMMRWISKRF-FQEVSTJZSA-N |
| InChi Code | InChI=1S/C25H31N3O5/c1-4-16-10-18(9-15(2)23(16)32-14-20(30)13-29)24-27-25(33-28-24)19-11-21(17-7-5-6-8-17)26-22(12-19)31-3/h9-12,17,20,29-30H,4-8,13-14H2,1-3H3/t20-/m0/s1 SMILES |
| Chemical Name | (2S)-3-[4-[5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl]-2-ethyl-6-methylphenoxy]propane-1,2-diol |
| Synonyms | ACT-334441; ACT334441; ACT 334441 |
| 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 | S1PR1 ( EC50 = 1 nM ); S1PR5 ( EC50 = 36 nM ); S1PR5 ( EC50 = 228 nM ); S1PR4 ( EC50 = 2134 nM ) |
| ln Vitro |
Cenerimod is a very strong S1P1 receptor agonist in (35S)-GTPγS assays utilizing preparations of HUVEC cell membranes, with an EC50 of 2 nM[1]. Cenerimod increases Ca2+ signaling and activates G protein in CHO cells, with EC50s of 1 nM and 124 nM, respectively[1]. Cenerimod (5 μM; 24 h) prevents fibroblasts from producing collagen[2]. |
| ln Vivo |
Cenerimod (0.1-10 mg/kg; a single p.o.) reversibly and dose-dependently decreases the number of circulating lymphocytes in rats[1]. Cenerimod (6 mg/kg/day for 30 days; p.o.) attenuates disease in a mouse experimental autoimmune encephalitis (EAE) model[1]. Cenerimod (10 mg/kg/day for 42 days; p.o.) reduces lung and skin fibrosis in Scl-cGVHD mice[2]. |
| Animal Protocol |
Male Wistar rats weighing 294-510 g 0.1, 0.3, 1, 3 and 10 mg/kg A single p.o. |
| References |
[1]. Cenerimod, a novel selective S1P 1 receptor modulator with unique signaling properties. Pharmacol Res Perspect. 2017 Dec;5(6):e00370. [2]. Attenuation of murine sclerodermatous models by the selective S1P 1 receptor modulator cenerimod. Sci Rep. 2019 Jan 24;9(1):658. |
| Additional Infomation |
Cenerimod has been used in trials studying the treatment of Systemic Lupus Erythematosus. Drug Indication Treatment of Systemic Lupus Erythematosus (SLE) |
Solubility Data
| Solubility (In Vitro) | DMSO: ~100 mg/mL (~220.5 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.51 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 25.0 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: ≥ 2.5 mg/mL (5.51 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 25.0 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 | 2.2049 mL | 11.0244 mL | 22.0488 mL | |
| 5 mM | 0.4410 mL | 2.2049 mL | 4.4098 mL | |
| 10 mM | 0.2205 mL | 1.1024 mL | 2.2049 mL |