1. Neuronal Signaling Cell Cycle/DNA Damage
  2. α-synuclein DNA/RNA Synthesis
  3. Synucleozid-2.0

Synucleozid-2.0 is a blood-brain barrier-permeable inhibitor that binds to the IRE of SNCA mRNA, with a EC50 of 2.9 µM and a Kd value of 1.8 µM. Synucleozid-2.0 selectively binds to and stabilizes the A bulge and adjacent closed base pairs in the 5' UTR IRE of SNCA mRNA, blocks the translation process and reduces intracellular levels of α-synuclein. Synucleozid-2.0 exerts cytoprotective effects against cytotoxicity induced by α-synuclein preformed fibrils. Synucleozid-2.0 is applicable to the research of Parkinson's disease.

For research use only. We do not sell to patients.

Synucleozid-2.0

Synucleozid-2.0 Chemical Structure

CAS No. : 613226-91-8

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Description

Synucleozid-2.0 is a blood-brain barrier-permeable inhibitor that binds to the IRE of SNCA mRNA, with a EC50 of 2.9 µM and a Kd value of 1.8 µM. Synucleozid-2.0 selectively binds to and stabilizes the A bulge and adjacent closed base pairs in the 5' UTR IRE of SNCA mRNA, blocks the translation process and reduces intracellular levels of α-synuclein. Synucleozid-2.0 exerts cytoprotective effects against cytotoxicity induced by α-synuclein preformed fibrils. Synucleozid-2.0 is applicable to the research of Parkinson's disease[1].

In Vitro

Synucleozid-2.0 selectively binds to the A bulge and its closed base pairs of SNCA IRE RNA, with a competitive Kd of 1.8 µM and an EC50 of 2.9 µM in fluorescence-based assays[1].
Synucleozid-2.0 (0.1-2 µM; 48 h) dose-dependently inhibits the translation of α-synuclein in SH-SY5Y cells with an IC50 of approximately 2 µM, but exerts no effect on the translation of ferritin, TfR or APP[1].
Synucleozid-2.0 (0.1-2 µM; 48 h) dose-dependently inhibits the translation driven by the internal ribosome entry site (IRE) of SNCA in HeLa cells in luciferase reporter assays, whereas it has no effect on reporter genes lacking the SNCA 5' UTR[1].
Synucleozid-2.0 (0.5-10 µM; 48 h) exerts dose-dependent cytoprotective effects on SH-SY5Y cells against α-synuclein PFF-induced toxicity, with an EC50 of 13 µM[1].
Synucleozid-2.0 (0.5-10 µM; 48 h) protects SNCA mRNA in SH-SY5Y cells from RNase H cleavage in a dose-dependent manner by binding to the A-bulge region targeted by Gapmer-1, but has no effect on gapmer-mediated cleavage targeting non-overlapping regions[1].
Synucleozid-2.0 (0-20 µM; 16 h) competes with Syn-ChemCLIP for binding to the same site on SNCA mRNA in SH-SY5Y cells[1].
Synucleozid-2.0 inhibits the translation of α-synuclein in SH-SY5Y cells by blocking the formation of preinitiation complex and preventing ribosome loading onto SNCA mRNA[1].
Synucleozid-2.0 (2 µM; 48 h) reduces α-synuclein levels by approximately 50% in both control and SNCA triplication patient-derived human dopaminergic neurons, without altering SNCA mRNA levels[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[1]

Cell Line: human dopaminergic neuroblastoma SH-SY5Y cells
Concentration: 0, 0.1, 0.5, 2 µM
Incubation Time: 48 h
Result: Dose-dependently inhibited α-synuclein translation with an IC50 of ~2 µM.
Had no effect on protein levels of ferritin, transferrin receptor (TfR), or amyloid precursor protein (APP).

Cell Cytotoxicity Assay[1]

Cell Line: SH-SY5Y cells
Concentration: 0, 0.5, 2, 10 µM
Incubation Time: 48 h
Result: Dose-dependently protected SH-SY5Y cells against PFF-induced toxicity, with significant cytoprotection observed at all tested concentrations.
Showed no toxicity with treatment alone.
Had an EC50 of 13 µM for cytoprotection.

ELISA Assay[1]

Cell Line: human iPSC-derived dopaminergic neurons (healthy control, Parkinson's disease patient with SNCA triplication)
Concentration: 2 µM
Incubation Time: 48 h
Result: Decreased α-synuclein protein levels by ~50% in both control dopaminergic neurons and patient-derived dopaminergic neurons with elevated α-synuclein levels.
Reduced patient-derived neuron α-synuclein levels to match untreated control neuron levels.
Had no effect on SNCA mRNA levels in these neurons.
Molecular Weight

506.38

Formula

C22H16BrN7OS

CAS No.
SMILES

O=C(NC1=CC2=C(C=C1)C=NN2)CSC3=NN=C(N3C4=CC=C(C=C4)Br)C5=CC=NC=C5

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Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (197.48 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.9748 mL 9.8740 mL 19.7480 mL
5 mM 0.3950 mL 1.9748 mL 3.9496 mL
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Complete Stock Solution Preparation Table

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.9748 mL 9.8740 mL 19.7480 mL 49.3700 mL
5 mM 0.3950 mL 1.9748 mL 3.9496 mL 9.8740 mL
10 mM 0.1975 mL 0.9874 mL 1.9748 mL 4.9370 mL
15 mM 0.1317 mL 0.6583 mL 1.3165 mL 3.2913 mL
20 mM 0.0987 mL 0.4937 mL 0.9874 mL 2.4685 mL
25 mM 0.0790 mL 0.3950 mL 0.7899 mL 1.9748 mL
30 mM 0.0658 mL 0.3291 mL 0.6583 mL 1.6457 mL
40 mM 0.0494 mL 0.2469 mL 0.4937 mL 1.2343 mL
50 mM 0.0395 mL 0.1975 mL 0.3950 mL 0.9874 mL
60 mM 0.0329 mL 0.1646 mL 0.3291 mL 0.8228 mL
80 mM 0.0247 mL 0.1234 mL 0.2469 mL 0.6171 mL
100 mM 0.0197 mL 0.0987 mL 0.1975 mL 0.4937 mL
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Product Name:
Synucleozid-2.0
Cat. No.:
HY-401209
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