SK-129
Based on 1 Customer Validation
SK-129 is a blood-brain barrier-permeable inhibitor of α-synuclein (αS) oligomers with a Kd of 221 nM. SK-129 preferentially binds to neurotoxic αS oligomers over physiological αS monomers, inhibits αS aggregation, blocks the interaction and co-aggregation of αS with tau protein, and prevents the maturation of αS-tau condensates into amyloid aggregates. SK-129 reduces ROS production, rescues dopaminergic neuron degeneration, improves motor function, restores endogenous dopamine synthesis, increases the number of Tyrosine Hydroxylase-positive neurons, prevents brain histopathological changes, alleviates neuroinflammation, and improves survival rates in relevant models. SK-129 can be used in research related to Parkinson's disease (PD) and Lewy body dementia (LBD).
For research use only. We do not sell to patients.
- Purity : 96.57%
- CAS No.: 1919889-97-6
- Formula: C51H42N8O15
- Molecular Weight:1006.92
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Storage:
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
All α-synuclein Isoforms
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Biological Activity
Description
In Vitro
SK-129 (SK-129F; 100 nM; until signal saturation) preferentially binds pathological αS oligomers and fibrils over physiological αS monomers, with a Kd value of 221 nM for αS oligomers[1].
SK-129 (10 μM; 12 h pre- or post-treatment) potently inhibits αS aggregation in αSA53T-YFP-expressing HEK293T cells mediated by NDE derived from Parkinson's disease (PD)[1].
SK-129 (1 μM) binds to αS-tau liquid condensates and inhibits their transition to toxic amyloid-like co-aggregates, instead inducing the formation of non-amyloid gel-like aggregates[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
| Species | Dose | Route | T1/2 | Cmax | Brain-to-Plasma Ratio |
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| Mice[1] | 20 mg/kg | i.v. | 1.78 (blood plasma) h | 139.8 (blood plasma) μg/mL | 9.4 % |
In Vivo
SK-129 (20 mg/kg; i.v.; every other day; 21 days) confers 100% survival up to 270 days, prevents PD-related weight loss, eliminates α-synuclein and α-synuclein-tau pathology, reduces neuroinflammation, and shows no systemic toxicity in the M83(A) mouse PD model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:UA196 (expresses human α-synuclein and GFP in DA neurons)[1]
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Dosage:25 μM; 50 μM
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Administration:administered on days 2 and 4 (early treatment); administered on day 5 (postdisease treatment)
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Result:Restored healthy DA neuron counts to 58.2 on day 5, 56.8 on day 10, and 56.5 on day 15 at 50 μM early treatment (untreated: 42.1, 20.5, 15.2 respectively).
Restored healthy DA neuron counts to 40 on day 5, 20 on day 10, and 15 on day 15 at 25 μM early treatment.
Restored motility to levels comparable to healthy N2 worms.
Reduced ROS-dependent fluorescence intensity compared to untreated worms.
Prevented further motility enhancement by dopamine supplementation, indicating restored endogenous dopamine synthesis.
Increased healthy DA neuron counts to 38.4 on day 15 at 50 μM postdisease treatment (untreated: 13.2).
Increased healthy DA neuron counts to 31.8 on day 15 at 25 μM postdisease treatment.
Improved motility and reduced ROS levels compared to untreated worms.
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Animal Model:M83(A) (transgenic expressing human A53T mutant α-synuclein; 8-week-old; stereotactic injection of postmortem PD brain-derived α-synuclein aggregates)[1]
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Dosage:20 mg/kg
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Administration:i.v.; every other day; 21 days (10 total doses)
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Result:Achieved weight gain comparable to control mice, whereas vehicle-treated mice exhibited progressive weight loss.
Conferred 100% survival up to 270 days with no motor impairment.
Eliminated detectable phosphorylated α-synuclein (αS-129), p62 aggregation, and microglial activation (Iba1 staining) at 6 and 9 months, whereas vehicle-treated mice had extensive pathology across multiple brain regions.
Showed no abnormalities in major organs via hematoxylin and eosin staining.
Prevented α-synuclein-tau coaggregates in the substantia nigra at 9 months, whereas vehicle-treated mice had clear coaggregation.
Chemical Information
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CAS No. 1919889-97-6
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Appearance Solid
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Molecular Weight 1006.92
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Formula C51H42N8O15
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SMILES
O=C(C1=NC2=C(NC(C3=NC4=C(NC(C5=NC6=C([N+]([O-])=O)C=CC=C6C(OC(C)C)=C5)=O)C=CC=C4C(OCC(O)=O)=C3)=O)C=CC=C2C(OC(C)C)=C1)NC7=C8C(C(OCC(O)=O)=CC(C(OC)=O)=N8)=CC=C7
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Solvent & Solubility
In Vitro:
DMSO : 12.5 mg/mL (12.41 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 1.25 mg/mL (1.24 mM); Clear solution
This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocols
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Neurotoxicity Study
This protocol assesses in vitro neurotoxicity by combining neuronal viability, mitochondrial/metabolic activity, neurite outgrowth, and optional neuronal network function readouts. Calcein-AM or resazurin/PrestoBlue readouts estimate viable or metabolically active cells; βIII-tubulin immunofluorescence detects neuronal morphology and neurite networks; TMRE detects mitochondrial membrane potential; and MEA recordings detect functional changes in neuronal network activity.
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ROS/oxidative-stress fluorescent staining
ROS/oxidative-stress fluorescent staining uses cell-permeant fluorogenic probes that become fluorescent after oxidation inside cells or tissues; commonly used examples include DCFH-DA/DCFDA for broad cellular oxidant detection, DHE for superoxide-related signal detection, MitoSOX for mitochondrial superoxide-related signal detection, and CellROX probes for oxidative-stress-associated fluorescence readouts. The assay detects probe oxidation rather than a single ROS species unless the probe and analysis method have been chemically validated for that species. DCFH-DA enters cells, is deacetylated by intracellular esterases to DCFH, and produces fluorescent DCF after oxidation, so the readout is used as an operational measure of total cellular oxidative stress rather than a species-specific ROS measurement. DHE and MitoSOX can report superoxide-related oxidation, but red fluorescence alone can include non-specific ethidium-like oxidation products; HPLC or optimized spectral approaches are
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Human pluripotent stem cell midbrain dopaminergic neuron differentiation
Human pluripotent stem cells are directed toward midbrain dopaminergic neurons by first inducing a neural floor-plate-like progenitor state, then patterning cells with ventralizing SHH signaling and midbrain/WNT-FGF cues, and finally maturing progenitors into neurons expressing dopaminergic markers such as TH, NURR1/NR4A2, PITX3, DAT/SLC6A3, VMAT2/SLC18A2, GIRK2/KCNJ6, FOXA2, LMX1A, and EN1. The main readouts are loss of pluripotency, acquisition of FOXA2+/LMX1A+ midbrain floor-plate progenitors, emergence of βIII-tubulin+/MAP2+ neurons, and production of TH+ dopaminergic neurons with molecular, dopamine-release, and electrophysiological features of midbrain dopaminergic identity.
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Research Protocol for Neurological Diseases
PINK1/Parkin-mediated mitophagy pathway is a mitochondrial quality-control signaling axis in which mitochondrial depolarization stabilizes PINK1 on damaged mitochondria, activates Parkin recruitment and E3 ubiquitin ligase activity, promotes ubiquitination of outer mitochondrial membrane proteins, recruits selective autophagy adaptors, and drives lysosomal degradation of damaged mitochondria. In neurological disease research, this pathway is experimentally important because neurons, especially dopaminergic neurons, are highly dependent on mitochondrial integrity, and defective mitochondrial turnover can lead to mitochondrial dysfunction, oxidative stress, impaired neuronal survival, α-synuclein accumulation, and neuroinflammatory damage-associated signals. The genetic disease link is strongest in Parkinson’s disease because mutations in PRKN/parkin cause autosomal recessive juvenile parkinsonism, mutations in PINK1 cause hereditary early-onset Parkinson’s disease, and Drosophila studie
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Amyloid: Congo Red Amyloid Staining
Congo red amyloid staining is a histochemical method used to detect extracellular amyloid deposits in tissue sections based on the affinity of Congo red dye for β-pleated sheet-rich protein aggregates. When bound to amyloid, Congo red produces characteristic apple-green birefringence under polarized light microscopy, which is widely regarded as a diagnostic feature of amyloid deposition in histopathology. The diagnostic principle relies on the combination of dye binding (congophilia) and optical anisotropy under polarized illumination, which distinguishes amyloid from most non-amyloid eosinophilic extracellular deposits in routine histological evaluation. Amyloid identification by Congo red staining remains a cornerstone in diagnostic pathology despite the availability of adjunct methods such as immunohistochemistry and mass spectrometry, particularly because of its ability to localize deposits directly within tissue architecture. The specificity of Congo red-positive deposits is incre
Purity & Documentation
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Data Sheet (279 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 0.9931 mL | 4.9656 mL | 9.9313 mL | 24.8282 mL |
| 5 mM | 0.1986 mL | 0.9931 mL | 1.9863 mL | 4.9656 mL | |
| 10 mM | 0.0993 mL | 0.4966 mL | 0.9931 mL | 2.4828 mL |
SK-129 Related Classifications
HY-182893 Related Classifications
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Keywords
- SK-129
- 1919889-97-6
- SK129
- SK 129
- α-synuclein
- Reactive Oxygen Species (ROS)
- Tyrosine Hydroxylase
- mouse brain homogenate
- blood-brain barrier
- α-synuclein oligomers
- iPSC midbrain dopaminergic neurons
- HEK293T cells
- parkinson’s disease
- C. elegans
- dopaminergic neuron
- human liver microsomes
- mouse plasma
- Inhibitor
- inhibitor
- inhibit