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SK-129

Cat No.:V145003 Purity: ≥98%
SK-129 is a blood-brain barrier permeable α-synuclein (αS) oligomer inhibitor with a dissociation constant (Kd) of 221 nM.
SK-129
SK-129 Chemical Structure CAS No.: 1919889-97-6
Product category: Hydroxylase
This product is for research use only, not for human use. We do not sell to patients.
Size Price
500mg
1g
Other Sizes
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Product Description
SK-129 is a blood-brain barrier-permeable α-synuclein (αS) oligomer inhibitor with a dissociation constant (Kd) of 221 nM. SK-129 preferentially binds to neurotoxic αS oligomers rather than physiological αS monomers, inhibiting αS aggregation, blocking the interaction and co-aggregation of αS with tau protein, and preventing αS-tau aggregates from maturing into amyloid aggregates. SK-129 can reduce the production of reactive oxygen species (ROS), rescue the degeneration of dopaminergic neurons, improve motor function, restore endogenous dopamine synthesis, increase the number of tyrosine hydroxylase-positive neurons, prevent pathological changes in brain tissue, alleviate neuroinflammation, and improve survival rates in relevant models. SK-129 can be used in research related to Parkinson's disease (PD) and Lewy body dementia (LBD).
Biological Activity I Assay Protocols (From Reference)
ln Vitro
SK-129 (SK-129F; 100 nM; until signal saturation) preferentially binds to pathological α-synuclein (αS) oligomers and fibrils rather than physiological αS monomers, with a dissociation constant (Kd) of 221 nM for αS oligomers [1]. SK-129 (10 μM; pretreatment or posttreatment for 12 hours) effectively inhibits the aggregation of αS in HEK293T cells expressing αSA53T-YFP mediated by neurotransmitters (NDE) of Parkinson's disease (PD) [1]. SK-129 (1 μM) binds to αS-tau liquid aggregates, inhibiting their conversion to toxic amyloid coagulates, and instead induces the formation of non-amyloid gel aggregates [1].
ln Vivo
SK-129 (25-50 μM; administered on days 2, 4 and 5) rescued dopaminergic neuronal degeneration, motor dysfunction, oxidative stress and behavioral deficits in the early and late stages of the UA196 Caenorhabditis elegans Parkinson's disease model in a dose-dependent manner [1]. SK-129 (20 mg/kg; intravenous injection; every other day; for 21 days) achieved 100% survival (up to 270 days) in the M83(A) mouse Parkinson's disease model, prevented Parkinson's disease-related weight loss, eliminated α-synuclein and α-synuclein-tau protein pathology, reduced neuroinflammation, and showed no systemic toxicity [1].
Animal Protocol
Animal/Disease Models:UA196 (expressing human α-synuclein and GFP in dopaminergic neurons) [1]
Doses: 25 μM; 50 μM
Route of Administration: Day 2 and 4 (early treatment); Day 5 (late disease treatment)
Experimental Results: After 50 μM early treatment, the number of healthy dopaminergic neurons recovered to 58.2 on day 5, 56.8 on day 10, and 56.5 on day 15 (compared to 42.1, 20.5, and 15.2 in the untreated group, respectively). After 25 μM early treatment, the number of healthy dopaminergic neurons recovered to 40 on day 5, 20 on day 10, and 15 on day 15. The levels recovered to those of healthy N2 nematodes. ROS-dependent fluorescence intensity was reduced compared to untreated nematodes. Dopamine supplementation prevented further enhancement of nematode motility, indicating that endogenous dopamine synthesis had been restored. On day 15 post-treatment, the number of healthy dopaminergic neurons increased to 38.4 at a concentration of 50 μM (compared to 13.2 in the untreated group). On day 15 post-treatment, the number of healthy dopaminergic neurons increased to 31.8 at a concentration of 25 μM. Compared to untreated nematodes, nematode motility was improved and ROS levels were reduced.
Animal/Disease Models:M83(A) (transgenic mice expressing human A53T mutant α-synuclein; 8 weeks old; stereotactic injection of α-synuclein aggregates derived from post-Parkinson's disease brain tissue) [1]
Doses: 20 mg/kg
Route of Administration: Intravenous injection; every other day; for 21 days (10 doses)
Experimental Results: The weight gain of the treated mice was comparable to that of the control mice, while the vector control mice showed progressive weight loss. The survival rate of the treated mice was 100%, with no motor dysfunction, and the survival time was up to 270 days. Phosphorylated α-synuclein (αS-129), p62 aggregation and microglial activation (Iba1 staining) were detectable in the treated mice at 6 and 9 months, while the vector control mice showed extensive pathological changes in multiple brain regions. Hematoxylin-eosin staining showed no abnormalities in the major organs. At 9 months, the formation of α-synuclein-tau protein co-aggregates in the substantia nigra of mice in the treatment group was inhibited, while significant co-aggregation was observed in mice in the vector control group.
References

[1]. Foldamers rescue synucleinopathy phenotypes in multiple in vitro and in vivo models. Sci Transl Med. 2026;18(843):eadu1050.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C51H42N8O15
Molecular Weight
1006.92
CAS #
1919889-97-6
Appearance
Typically exists as solids at room temperature
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
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 Data
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
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
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*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 : PEG300Tween 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).
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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL 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).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 0.9931 mL 4.9656 mL 9.9313 mL
5 mM 0.1986 mL 0.9931 mL 1.9863 mL
10 mM 0.0993 mL 0.4966 mL 0.9931 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.

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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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