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SA4503 dihydrochloride
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
SA4503 dihydrochloride图片
CAS NO:165377-44-6
规格:≥98%
包装与价格:
包装价格(元)
2mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
SA4503 dihydrochloride (also known as AGY94806 dihydrochloride and Cutamesine dihydrochloride), is a potent sigma-1 (σ1) receptor agonist with an IC50 of 17.4 nM in guinea pig brain membranes. It is under development for recovery enhancement after acute ischemic stroke. SA4503 protects motor neuron NSC34 cells against superoxide dismutase 1 and serum free neurotoxicity. It upregulates the phosphorylation levels of Akt and extracellular signal-regulated kinase (ERK) 1/2. SA-4503 protects against retinal cell death in vitro and in vivo by the agonistic effect of σ1 receptor. Therefore, σ1 receptor may serve as a potential therapeutic target in retinal diseases mediated by photoreceptor degeneration.
理化性质和储存条件
Molecular Weight (MW) 441.43
Formula C23H34Cl2N2O2
CAS No. 165377-44-6 (HCl);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 30 mg/mL
Water: < 1 mg/mL
Ethanol: < 1 mg/mL
SMILES Code COC1=CC=C(C=C1OC)CCN2CCN(CCCC3=CC=CC=C3)CC2.[H]Cl.[H]Cl
Synonyms SA4503; SA 4503; SA-4503; AGY94806; AGY-94806; AGY 94806; Cutamesine HCl
实验参考方法
In Vitro

In vitro activity: SA4503 protects motor neuron NSC34 cells against superoxide dismutase 1 and serum free neurotoxicity. It upregulates the phosphorylation levels of Akt and extracellular signal-regulated kinase (ERK) 1/2.The sigma receptor might be involved in several diseases in the central nervous system. SA4503, a potent σ1receptor agonist, has 103-fold higher affinity for σ1 (IC50=17.4 nM) than σ2 (IC50=1,784 nM) sites in guinea pig brain membranes. SA4503 is 14-fold selective for σ1 (Ki=4.6 nM) over σ2 (Ki=63.1 nM) sites in guinea pig brain homogenates.


Kinase Assay: SA4503, a potent sigma(1) receptor agonist, is reported as having 103-fold higher affinity for sigma(1) (IC(50) = 17.4 nM) than sigma(2) (IC(50) = 1,784 nM) sites in guinea pig brain membranes. Modest structural changes appear to have major effects on sigma(1)/sigma(2) selectivity. The fluoroethyl analog, FE-SA4503, is described as having high primary affinity for sigma(2) sites (IC(50) = 2.11 nM) and a weaker interaction with sigma(1) sites (IC(50) = 6.48 nM). SA4503 and FE-SA4503 have been radiolabeled for PET studies, and both bind selectively to sigma(1) receptors in animal and human brain in vivo. We prepared SA4503 and FE-SA4503 as reference compounds for radioligand development efforts. In our hands, SA4503 is 14-fold selective for sigma(1) (K(i) = 4.6 nM) over sigma(2) (K(i) = 63.1 nM) sites in guinea pig brain homogenates. Further, FE-SA4503 exhibits the same 14-fold selectivity for sigma(1) (K(i) = 8.0 nM) over sigma(2) (K(i) = 113.2 nM) receptors. The main differences from previously reported values stem from sigma(2) affinity determinations. This protocol, displacement of [(3)H]DTG binding to sigma(2) sites using (+)-pentazocine (200 nM) to mask sigma(1) sites, was validated by the proper rank order of sigma(2) inhibitory potencies shown by a panel of additional ligands: ifenprodil> haloperidol> DTG>> (+)-pentazocine. Robust Pearson correlation (r = 1.0, P = 0.002; slope = 0.97) was observed for our pK(i) values against those from a prior study by others. The findings have bearing on structure-activity relationships for this active series, and on conclusions that might be drawn from experiments relying upon defined sigma(1)/sigma(2) binding selectivity.


Cell Assay:The NSC34 cells are seeded at a density of 7000 cells per well into 96-well plates with D-MEM and transfected using Lipofectamine 2000 mixed with 2 μg /mL of plasmid vector in D-MEM for 6 h. After 6 h, the cell-culture medium is replaced with fresh D-MEM and culture and allowed to proceed for a further 42 h. The cells are then transferred to serum-free D-MEM and immediately treated with SA4503 at a final concentration of 1, 3, or 10 nM.

In VivoSA4503 extends the survival time in the SOD1G93A mice
Animal model SOD1G93A mice
Formulation & Dosage
References Neurosci Lett. 2010 Jan 29;469(3):303-8; Synapse. 2006 May;59(6):350-8.