Synucleozid dihydrochloride

Synucleozid (NSC 377363) is a potent inhibitor of the SNCA mRNA that encodes α-synuclein protein (IC50=1.5 μM). 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[1].

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

Research Areas >> Neurological Disease

IC50: 1.5 μM (SNCA IRE RNA)[1]

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[1]. 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 IC50 of 500 nM, and inhibits α-synuclein protein expression in SH-SY5Y neuroblastoma cells[1]. 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 EC50 value of 2.7 μM, 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 μM[1]. 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[1]. Cell Viability Assay[1] Cell 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 Analysis[1] Cell 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.

[1]. Zhang P, et al. Translation of the intrinsically disordered protein α-synuclein is inhibited by a small molecule targeting its structured mRNA.Proc Natl Acad Sci U S A. 2020 Jan 21;117(3):1457-1467.