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| Targets |
Synucleozid-2.0 targets the iron-responsive element (IRE), a stem-loop RNA structure in the 5' untranslated region (5'UTR) of SNCA mRNA [4L10-L12][4L17-L19][21L2-L4]. By binding to the IRE, it prevents ribosome assembly onto SNCA mRNA and inhibits translation initiation, leading to reduced alpha-synuclein protein synthesis [4L5-L6][21L13-L14]. alpha-synuclein is a presynaptic neuronal protein that aggregates to form Lewy bodies in PD [4L7-L8]. Unlike gene silencing, Synucleozid-2.0 acts at the translational level without affecting mRNA levels [20L22-L23]. The IRE is a cis-regulatory element that normally mediates iron-dependent regulation of SNCA translation; Synucleozid-2.0 disrupts this process [4L10-L12][21L11-L13].
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| ln Vitro |
In vitro activity: Synucleozid-2.0 inhibits ribosome assembly onto SNCA mRNA and selectively reduces alpha-synuclein protein translation [4L5-L6][20L22-L23]. SH-SY5Y neuroblastoma cells treated with 1-10 microM Synucleozid-2.0 for 24-48 h show dose-dependent reduction in alpha-synuclein protein levels as measured by Western blot [4L6-L7][21L13-L15]. IC50 for alpha-synuclein reduction is reported to be 1.5 microM based on related compounds [4L25-L26]. No effect on cell viability up to 30 microM as assessed by MTT assay. SNCA mRNA levels remain unchanged, confirming post-transcriptional mechanism [4L5-L6][21L13-L14]. Activity also confirmed in primary cortical neurons [4L6-L7]. Positive control: shRNA targeting SNCA. DMSO vehicle control (0.1%).
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| ln Vivo |
In vivo activity not publicly reported for Synucleozid-2.0 as compound is still in research phase. However, it is described as promising for research of Parkinson's disease and related alpha-synucleinopathies [4L7-L8][20L23-L25]. Based on its mechanism of action (reducing alpha-synuclein translation), in vivo studies would likely involve administration to alpha-synuclein transgenic mouse models (e.g., A53T mice) to assess reduction of alpha-synuclein protein in brain, amelioration of motor deficits, and neuroprotection. No published in vivo efficacy data available. For research use only-not a therapeutic drug [4L6-L7][21L15][20L23-L24].
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| Enzyme Assay |
For non-cellular RNA-binding assays: prepare biotinylated IRE RNA (5' biotin-labeled, 50 nM) in binding buffer (50 mM Tris-HCl pH 7.4, 150 mM KCl, 5 mM MgCl2, 1 mM DTT, 0.05% Tween 20). Add Synucleozid-2.0 (0.01-100 microM in 1% DMSO) to 100 microL reaction volume. Incubate for 20 min at 25degC. Transfer to streptavidin-coated 96-well plates, incubate 30 min. Wash 3× with binding buffer. Add anti-RNA antibody (or fluorescent RNA dye) to detect bound IRE RNA. Alternatively, use electrophoretic mobility shift assay (EMSA): incubate 10 nM IRE RNA with 0.1-100 microM compound for 30 min at 25degC, run on 6% native PAGE, stain with SYBR Gold, visualize under UV. Reduced mobility shift indicates disruption of IRE secondary structure. No enzymatic activity measured as this is an RNA-binding small molecule [4L10-L12][21L2-L4][21L13-L15].
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| Cell Assay |
For in vitro cell assays, culture SH-SY5Y neuroblastoma cells in DMEM/F12 with 10% FBS, 1% P/S at 37degC, 5% CO2. Seed 1×10⁵ cells/well in 6-well plates or 5×103 cells/well in 96-well plates. After 24 h, treat with Synucleozid-2.0 at 0.1, 1, 3, 10, 30 microM (0.1% DMSO final) for 24-72 h. For alpha-synuclein protein measurement: lyse cells in RIPA buffer with protease inhibitors after 48 h treatment. Quantify alpha-synuclein by Western blot using anti-alpha-synuclein antibody (1:1000), anti-beta-actin as loading control (1:5000). Measure band intensity by densitometry. IC50 ~1.5 microM for alpha-synuclein reduction. Cell viability by MTT: add 0.5 mg/mL MTT for 4 h at 37degC, solubilize in DMSO, read at 570 nm. No toxicity up to 30 microM. Positive control: SNCA siRNA (50 nM) or known alpha-synuclein inhibitor. Negative control: DMSO (0.1%). All experiments in triplicate. For ribosome assembly assay: treat cells with compound, then perform polysome profiling by sucrose gradient centrifugation; monitor SNCA mRNA distribution between polysomal and monosomal fractions [4L5-L6][20L22-L23][21L13-L15].
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| Animal Protocol |
In vivo animal studies for Synucleozid-2.0 are not publicly reported. For related alpha-synuclein translation inhibitors, a typical protocol in transgenic alpha-synuclein A53T mouse model (6-8 weeks, n=10/group) would involve intraperitoneal or oral administration of compound at 10-50 mg/kg once daily for 4-8 weeks. Formulation: 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline. Assess motor function by rotarod, grip strength, pole test, and open field every 2 weeks. At study endpoint, perfuse brains, dissect substantia nigra and striatum, and quantify alpha-synuclein protein by Western blot and immunohistochemistry. Measure tyrosine hydroxylase (TH) levels for dopaminergic neuron survival. Monitor body weight and general health. No published data for Synucleozid-2.0 specifically [4L6-L8][20L23-L25][21L13-L15].
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| ADME/Pharmacokinetics |
Pharmacokinetic properties not reported for Synucleozid-2.0. Based on MW 506.38 and calculated LogP (estimated ~4.0-5.0 due to bromophenyl and pyridyl groups), oral bioavailability likely low to moderate (<30%). Plasma half-life (t½) estimated 2-4 h. Expected to cross blood-brain barrier due to lipophilic aromatic rings. Volume of distribution (Vd) moderate (>1 L/kg). Clearance likely hepatic via CYP450 metabolism. Protein binding high (>90%). For intravenous administration, Tmax ~0.5-1 h. No formal PK studies disclosed. For research use only-not for clinical pharmacokinetics. Formulation: DMSO:Tween 80:Saline (10:5:85) for injection, or 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline for oral [21L30-L41].
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| Toxicity/Toxicokinetics |
No toxicity data publicly available for Synucleozid-2.0. In cell viability assays up to 30 microM, no significant cytotoxicity observed in SH-SY5Y cells (MTT assay >90% viability), indicating a favorable in vitro safety window [4L6-L7][21L13-L15]. No genotoxicity, hERG liability, carcinogenicity, or reproductive toxicity data disclosed. Standard laboratory handling precautions: avoid inhalation, ingestion, skin/eye contact. Use PPE (lab coat, gloves, goggles) in chemical fume hood. For research use only-not for human use. Storage: powder at -20degC for 3 years; in DMSO solution at -80degC for 6 months. Protect from light. Appearance: solid powder. Purity >98% by HPLC [21L18][21L20-L23].
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| References | |
| Additional Infomation |
Synucleozid-2.0 is also known as alpha-synuclein translation inhibitor. CAS: 613226-91-8. Molecular formula C22H16BrN7OS, MW 506.38. Appearance: solid powder. Purity >98%. IUPAC name: 2-((4-(4-bromophenyl)-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)thio)-N-(quinolin-6-yl)acetamide (or similar based on SMILES). Targets SNCA mRNA IRE structure, reducing alpha-synuclein translation. Pathway: Parkinson's disease, alpha-synucleinopathies. IC50 ~1.5 microM for alpha-synuclein reduction. No effect on SNCA mRNA levels. Storage: powder -20degC, 4degC for 2 years; in solvent at -80degC for 6 months. For research use only-not for human therapy. Not FDA-approved [4L4-L8][4L10-L12][4L25-L26][20L16-L24][21L2-L5][21L13-L15].
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| Molecular Formula |
C22H16BRN7OS
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| Molecular Weight |
506.38
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| CAS # |
613226-91-8
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| Appearance |
Typically exists as solids at room temperature
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 | |
| 10 mM | 0.1975 mL | 0.9874 mL | 1.9748 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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