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Art. -Nr.: HY-182893

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SK-129

SK-129 is a blood-brain barrier-permeable inhibitor of α-synuclein (αS) oligomers with a K_d 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).

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CAS. Nr.: 1919889-97-6
Formel: C₅₁H₄₂N₈O₁₅
Molecular Weight:1006.92

Speicherung:

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

SK-129 Chemical Structure

CAS. Nr.: 1919889-97-6

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

Alle α-synuclein Isoform-spezifische Produkte anzeigen :

In Vitro

SK-129 (SK-129_F; 100 nM; until signal saturation) preferentially binds pathological αS oligomers and fibrils over physiological αS monomers, with a K_d value of 221 nM for αS oligomers^[1].
SK-129 (10 μM; 12 h pre- or post-treatment) potently inhibits αS aggregation in αS^A53T-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.

Parmacokinetics

Species	Dose	Route	T_1/2	C_max	Brain-to-Plasma Ratio
Mice^[1]	20 mg/kg	i.v.	1.78 (blood plasma) h	139.8 (blood plasma) μg/mL	9.4 %

In Vivo

SK-129 (25-50 μM; administered on days 2 and 4, day 5) rescues DA neuron degeneration, motor deficits, oxidative stress, and behavioral deficits in both early and postdisease UA196 C. elegans PD models in a dose-dependent manner^[1].
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.

Animal Model:

UA196 (expresses human α-synuclein and GFP in DA neurons)^[1]
Dosage:

25 μM; 50 μM
Administration:

administered on days 2 and 4 (early treatment); administered on day 5 (postdisease treatment)
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.

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]
Dosage:

20 mg/kg
Administration:

i.v.; every other day; 21 days (10 total doses)
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

CAS. Nr. 1919889-97-6
Molecular Weight 1006.92
Formel C₅₁H₄₂N₈O₁₅
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
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

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

Reinheit & Dokumentation

Handling Instructions (2659 KB)

Verweise

[1]. Dohoney RA, et al. Foldamers rescue synucleinopathy phenotypes in multiple in vitro and in vivo models. Sci Transl Med. 2026;18(843):eadu1050. [Content Brief]

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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100 mg

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Biologische Aktivität
- Beschreibung
- In Vitro
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise

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SK-129

Alle α-synuclein Isoform-spezifische Produkte anzeigen