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在色谱分析、有机合成和交叉偶联反应领域已被 0 篇同行评审文献引用。
Synucleozid hydrochloride (NSC 377363 hydrochloride) is a potent inhibitor of the SNCA mRNA that encodes α-synuclein protein. Synucleozid selectively targets the α-synuclein mRNA 5′ UTR at the designed IRE site, decreases the amount of SNCA mRNA loaded into polysomes and thereby inhibits SNCA translation. Synucleozid has the potential for the investigation of Parkinson’s disease.
In Vitro
Synucleozid (0.25-1 μM; 24 hours) abrogates cytotoxicity induced by α-synuclein preformed fibrils, which act as seeds and recruit endogenous α-synuclein to aggregate. Synucleozid (0-1 μM; 24 hours) binds to the A bulge near the base of the IRE hairpin, reduced levels of α-synuclein in a dose-dependent manner with an IC 50 of 500 nM, and inhibits α-synuclein protein expression in SH-SY5Y neuroblastoma cells. Synucleozid (100 nM-100 μM; 24 hours) binds to 2-AP-labeled and native IRE RNA with similar affinities. It decreases 2-AP emission with an EC 50 value of 2.7 ± 0.4 μM, recovery of 2-AP emissions is observed as a function of unlabeled SNCA IRE RNA (RNA-0) concentration, affording a competitive K d of 1.5 ± 0.3 μM. Synucleozid (0.25-1 μM; 24 hours) decreases α-synuclein and other proteins that have IREs in their mRNA’s UTR including APP, PrP, Ferritin and TfR as a dose-dependent mannner. All panels is completed in SH-SY5Y cells, except for PrP protein which is assessed in Neuro-2A cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: SH-SY5Y neuroblastoma cells Concentration: 0.25 μM, 0.5 μM, 1 μM Incubation Time: 24 hours Result: Decreased LDH release as a dose-dependent manner. Western Blot AnalysisCell Line: SH-SY5Y neuroblastoma cells Concentration: 0.25 μM, 0.5 μM, 1 μM Incubation Time: 24 hours Result: Decreased α-synuclein expression as a concentration-dependent manner.
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