Synucleozid dihydrochloride

– Synucleozid hydrochloride (NSC 377363 hydrochloride) is a potent inhibitor of the SNCA mRNA that encodes alpha-synuclein protein (IC50=1.5 uM). Synucleozid selectively targets the alpha-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[1]. IC50 & Target: IC50: 1.5 uM (SNCA IRE RNA)[1] In Vitro: Synucleozid (0.25-1 uM; 24 hours) abrogates cytotoxicity induced by alpha-synuclein preformed fibrils, which act as seeds and recruit endogenous alpha-synuclein to aggregate[1]. Synucleozid (0-1 uM; 24 hours) binds to the A bulge near the base of the IRE hairpin, reduced levels of alpha-synuclein in a dose-dependent manner with an IC50 of 500 nM, and inhibits alpha-synuclein protein expression in SH-SY5Y neuroblastoma cells[1]. Synucleozid (100 nM-100 uM; 24 hours) binds to 2-AP-labeled and native IRE RNA with similar affinities. It decreases 2-AP emission with an EC50 value of 2.7 uM, recovery of 2-AP emissions is observed as a function of unlabeled SNCA IRE RNA (RNA-0) concentration, affording a competitive Kd of 1.5 uM[1]. Synucleozid (0.25-1 uM; 24 hours) decreases alpha-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[1].