[CAS NO. 1094042-01-9] CYM5442
PRODUCTS SPECIFICATIONS [1094042-01-9]
DESCRIPTION [1094042-01-9]
Overview
| MDL | MFCD12912402 |
|---|---|
| Molecular Weight | 409.48 |
| Molecular Formula | C23H27N3O4 |
| SMILES | CCOC1=CC=C(C2=NC(C3=CC=CC4=C3CCC4NCCO)=NO2)C=C1OCC |
Summary
CYM5442 is a potent, highly-selective and orally active sphingosine 1-phosphate (S1P1) receptor agonist with an EC 50 of 1.35 nM. CYM5442 is inactive against S1P2, S1P3, S1P4, and S1P5. CYM5442 activates S1P1 -dependent p42/p44-MAPK phosphorylation. CYM5442 exerts retinal neuroprotection. CYM5442 can easily penetrate the central nervous system (CNS) [1] [2] .
IC50 & Target
EC50: 1.35 nM (Sphingosine 1-phosphate (S1P1) receptor) [1]
In Vitro
CYM5442 (0.5 µM; 0-60 minutes; HEK293 cells) treatment stimulates S1P1 phosphorylation in a time-dependent manner in P32-orthophosphate labeled cells
[1]
.
CYM5442 activates S1P1-dependent p42/p44-MAPK phosphorylation in CHO-K1 cells transfected with S1P1 with an EC
50
of 46 nM. The R120 for alanine (R120A) mutant is still able to maintain p42/p44-MAPK activity when incubated with CYM5442 (EC
50
of 67 nM). Activation of p42/p44-MAPK by CYM5442 in E121A S1P1 cells is concentration dependent, with a mean EC
50
value of 134 nM
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis [1]
| Cell Line: | HEK293 cells stably expressing S1P1 fused to GFP on the carboxy-terminus |
| Concentration: | 0.5 µM |
| Incubation Time: | 0 minutes, 2 minutes, 5 minutes, 10 minutes, 30 minutes, 60 minutes |
| Result: | Stimulated S1P1 phosphorylation in a time-dependent manner. |
In Vivo
CYM5442 (1 mg/kg; intraperitoneal injection; daily; for 5 days; adult male albino Wistar rats) treatment shows preserved visual function of visual evoked potentials (VEP). Retinal nerve fiber layer (RNFL) is significantly thicker in the CYM treated-animals compared to the vehicle [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Adult male albino Wistar rats (8-10 weeks old; 180-230 g) infected ocular endothelin-1 (ET-1) [2] |
| Dosage: | 1 mg/kg |
| Administration: | Intraperitoneal injection; daily; for 5 days |
| Result: | Visual evoked potentials (VEP) showed preserved visual function. Showed significantly higher retinal ganglion cells (RGCs) numbers. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 2.63 mg/mL ( 6.42 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.4421 mL | 12.2106 mL | 24.4212 mL |
| 5 mM | 0.4884 mL | 2.4421 mL | 4.8842 mL |
| 10 mM | --- | --- | --- |
References
- [1] Gonzalez-Cabrera PJ, et al. Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P-like headgroup interactions. Mol Pharmacol. 2008 Nov;74(5):1308-18.
- [2] Blanco R, et al. The S1P1 receptor-selective agonist CYM-5442 protects retinal ganglion cells in endothelin-1 induced retinal ganglion cell loss. Exp Eye Res. 2017 Nov;164:37-45.
