CYM5442

Names

[ Name ]:
CYM5442

[Synonym ]:
CYM-5442
2-(4-(5-(3,4-diethoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl amino) ethanol
2-(4-(5-(3,4-Diethoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ylamino)ethanolhydrochloride
CYM5442

Biological Activity

[Description]:

CYM5442 is a potent, highly-selective and orally active sphingosine 1-phosphate (S1P1) receptor agonist with an EC50 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].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> LPL Receptor

Research Areas >> Neurological Disease

[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 EC50 of 46 nM. The R120 for alanine (R120A) mutant is still able to maintain p42/p44-MAPK activity when incubated with CYM5442 (EC50 of 67 nM). Activation of p42/p44-MAPK by CYM5442 in E121A S1P1 cells is concentration dependent, with a mean EC50 value of 134 nM[1]. 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]. 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.

[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.

Chemical & Physical Properties

[ Molecular Formula ]:
C₂₃H₂₇N₃O₄

[ Molecular Weight ]:
409.47800

[ Exact Mass ]:
409.20000

[ PSA ]:
89.64000

[ LogP ]:
4.16110

[ Storage condition ]:
-20℃

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

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Related Compounds

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