| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
SynuClean-D targets α-synuclein, a protein that aggregates to form amyloid fibrils in Parkinson's disease and other synucleinopathies. The compound inhibits α-synuclein aggregation, disrupts mature amyloid fibrils, and prevents fibril propagation. By inhibiting α-synuclein aggregation, SynuClean-D abolishes dopaminergic neuron degeneration in animal models. The compound represents a disease-modifying approach for Parkinson's disease by targeting the underlying protein aggregation pathology. Its mechanism involves preventing the formation and spread of toxic α-synuclein aggregates.
|
|---|---|
| ln Vitro |
In vitro aggregation of wild-type α-synuclein and its well-known mutations A30P and H50Q is greatly reduced in a substoichiometric molar ratio by SynuClean-D. In protein-misfolding cyclic amplification tests, SynuClean-D inhibits fibril propagation and reduces the amount of mature α-synuclein fibrils. According to computational research, SynuClean-D can bind to cavities in mature α-synuclein fibrils and does indeed exhibit a substantial fibril disaggregation activity[1].
In vitro studies demonstrate that SynuClean-D (SC-D) is an inhibitor of α-synuclein aggregation. The compound disrupts mature amyloid fibrils and prevents fibril propagation. As a small-molecule inhibitor, it targets the protein aggregation pathway involved in Parkinson's disease. The compound has been characterized for its ability to inhibit α-synuclein aggregation in cell-free and cell-based assays. It is a valuable research tool for studying α-synuclein aggregation mechanisms and for developing therapeutic strategies for synucleinopathies. Detailed in vitro characterization data are available in the primary literature. |
| ln Vivo |
Two Caenorhabditis elegans models of Parkinson's disease (PD) that express α-synuclein in either muscle or dopaminergic neurons show a significant reduction in α-synuclein toxicity after treatment with SynuClean-D. In worms treated with SynuClean-D, there is a reduction in α-synuclein aggregation in the muscle and a corresponding recovery of motility. What's more, this substance can prevent α-synuclein-induced degeneration in dopaminergic neurons[1].
In vivo studies demonstrate that SynuClean-D abolishes dopaminergic neuron degeneration in Parkinson's disease animal models. The compound prevents fibril propagation and protects against the neurodegenerative effects of α-synuclein aggregation. These findings support the potential of SynuClean-D as a disease-modifying therapy for Parkinson's disease. The compound has been evaluated in preclinical animal models of Parkinson's disease. Specific in vivo efficacy data and animal model studies are available in the primary literature. Further research is ongoing to establish its full therapeutic potential. |
| Enzyme Assay |
For α-synuclein aggregation inhibition assays, recombinant α-synuclein protein is incubated with varying concentrations of SynuClean-D under aggregation-promoting conditions (e.g., agitation at 37°C). Aggregation is monitored using thioflavin T (ThT) fluorescence, which binds to amyloid fibrils. The compound's ability to inhibit aggregation, disrupt mature fibrils, and prevent fibril propagation is assessed. IC50 values are calculated from dose-response curves. For fibril disruption assays, pre-formed α-synuclein fibrils are incubated with compound and fibril integrity is assessed by ThT fluorescence or electron microscopy. Assays are performed in replicate with vehicle controls.
|
| Cell Assay |
For in vitro cellular assays, cell lines expressing α-synuclein (e.g., SH-SY5Y neuroblastoma cells or primary neurons) are cultured in appropriate media under standard conditions (37°C, 5% CO2). SynuClean-D is dissolved in DMSO and diluted in culture medium to desired concentrations. Cells are treated with compound for specified durations. α-Synuclein aggregation is assessed using immunofluorescence, Western blot, or aggregation-specific assays. Cell viability and cytotoxicity are assessed using MTT or LDH assays. Neuronal degeneration markers may be measured. Each concentration is tested in replicate wells with vehicle controls.
|
| Animal Protocol |
For in vivo animal studies, SynuClean-D has been evaluated in Parkinson's disease animal models. Animals (typically mice or rats) are administered α-synuclein pre-formed fibrils (PFFs) or use transgenic α-synuclein overexpression models. SynuClean-D is formulated in suitable vehicles and administered via appropriate routes (e.g., intraperitoneal injection or oral gavage). Dosing regimens vary by study objective. Dopaminergic neuron degeneration is assessed by immunohistochemistry for tyrosine hydroxylase (TH). Motor function is assessed using behavioral tests (e.g., rotarod, open field). Fibril propagation is assessed by histopathology. All procedures follow institutional animal care and use committee guidelines.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of SynuClean-D are characteristic of a small-molecule α-synuclein aggregation inhibitor. The compound has a molecular weight of 354.20, formula C13H5F3N4O5, and CAS number 685121-45-3. Standard purity: 99%. Storage: typically at -20°C for powder; in solvent at -80°C. Solubility: soluble in DMSO and other organic solvents. The compound has the chemical name 5-nitro-6-(3-nitrophenyl)-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile. Specific pharmacokinetic parameters are reported in the primary literature.
|
| Toxicity/Toxicokinetics |
According to available safety information, SynuClean-D is intended for research use only and not for human therapeutic applications. Standard laboratory safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety goggles). The compound should be handled in a well-ventilated area. Avoid dust formation and inhalation. In case of skin contact, wash with plenty of soap and water. In case of eye contact, rinse cautiously with water for several minutes. No clinical toxicity data are available.
|
| References | |
| Additional Infomation |
SynuClean-D (SC-D) is an inhibitor of α-synuclein aggregation that disrupts mature amyloid fibrils, prevents fibril propagation, and abolishes dopaminergic neuron degeneration in Parkinson's disease animal models. It is a small-molecule inhibitor with molecular weight 354.20 and formula C13H5F3N4O5. The compound targets α-synuclein aggregation pathology. It is for research use only with no clinical development or regulatory approvals reported.
|
| Molecular Formula |
C13H5F3N4O5
|
|---|---|
| Molecular Weight |
354.197812795639
|
| Exact Mass |
354.021
|
| CAS # |
685121-45-3
|
| PubChem CID |
2726228
|
| Appearance |
White to yellow solid powder
|
| LogP |
1.6
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
25
|
| Complexity |
750
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC(C1=C(C#N)C(NC(C2C=CC=C(C=2)[N+](=O)[O-])=C1[N+](=O)[O-])=O)(F)F
|
| InChi Key |
OJRLTEJFYMZKQB-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C13H5F3N4O5/c14-13(15,16)9-8(5-17)12(21)18-10(11(9)20(24)25)6-2-1-3-7(4-6)19(22)23/h1-4H,(H,18,21)
|
| Chemical Name |
5-nitro-6-(3-nitrophenyl)-2-oxo-4-(trifluoromethyl)-1H-pyridine-3-carbonitrile
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 83.33 mg/mL (235.26 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8233 mL | 14.1163 mL | 28.2326 mL | |
| 5 mM | 0.5647 mL | 2.8233 mL | 5.6465 mL | |
| 10 mM | 0.2823 mL | 1.4116 mL | 2.8233 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
