PROTAC α-synuclein degrader 5
Based on 1 Customer Validation
PROTAC α-synuclein degrader 5 is a selective PROTAC degrader targeting α‑synuclein aggregates, with a DC50 of 7.51 μM. PROTAC α-synuclein degrader 5 binds to αSyn aggregates, recruits the CRBN E3 ubiquitin ligase, and mediates the ubiquitination and subsequent degradation of α‑synuclein aggregates. PROTAC α-synuclein degrader 5 activates the autophagy-lysosome pathway. PROTAC α-synuclein degrader 5 reduces ROS levels in neuroblastoma cells, restores mitochondrial membrane potential, rescues cell viability, and decreases LDH release. PROTAC α-synuclein degrader 5 degrades αSyn aggregates in Caenorhabditis elegans and ameliorates oxidative stress. PROTAC α-synuclein degrader 5 is used for the research of synucleinopathies, such as Parkinson's disease.
(Pink: α-synuclein ligand (HY-187000); Blue: VHL ligand (HY-10984); Black: linker).
For research use only. We do not sell to patients.
- Purity: 99.80%
- CAS No.: 2781922-42-5
- Formula: C39H41N7O10
- Molecular Weight:767.78
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Storage:
-20°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
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
α-synuclein Aggregation 7.51 μM (DC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| HEK-293T | DC50 |
7.51 μM
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Degradation of αSyn aggregates in pre-formed fibril-seeding Snca OE HEK293T human embryonic kidney cells assessed by immunoblot assay after 48 h incubation.
Degradation of αSyn aggregates in pre-formed fibril-seeding Snca OE HEK293T human embryonic kidney cells assessed by immunoblot assay after 48 h incubation.
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37267712 |
| HEK-293T | DC50 |
3.32 μM
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Degradation of conformation-specific αSyn aggregates in pre-formed fibril-seeding Snca OE HEK293T human embryonic kidney cells assessed by conformation-specific native dot blot assay after 48 h incubation.
Degradation of conformation-specific αSyn aggregates in pre-formed fibril-seeding Snca OE HEK293T human embryonic kidney cells assessed by conformation-specific native dot blot assay after 48 h incubation.
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37267712 |
In Vitro
PROTAC α-synuclein degrader 5 (Compound 2b) (0.625‑20 μM; 0-48 h) degrades α-synuclein aggregates in the Snca OE-PFF seeding model HEK293T cells, with a DC50 of 7.51 μM and a Dmax of 89%. It exhibits high selectivity for aggregated α-synuclein and does not affect the level of α-synuclein monomers[1].
PROTAC α-synuclein degrader 5 (1 μM) exhibits a binding dissociation constant KD of 1.161 μM toward α-synuclein preformed fibrils (PFF) as determined by fluorescence polarization assay[1].
PROTAC α-synuclein degrader 5 (10 μM; 12 h) is confirmed via co-immunoprecipitation (co-IP) assay to increase the ubiquitination level of α-synuclein aggregates in HEK293T cells of the Snca OE-PFF seeding model[1].
PROTAC α-synuclein degrader 5 (10 μM; 48 h) achieves the degradation of α-synuclein aggregates in the Snca OE-PFF seeding model HEK293T cells via the combined action of the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway (ALP); after treatment with MG132 (HY-13259), BafA1 (HY-100558) or LC3B knockdown, the degradation efficiency decreases significantly[1].
PROTAC α-synuclein degrader 5 (10 μM; 6 h) activates autophagic flux and promotes lysosome biogenesis in the Snca OE-PFF seeding model of HEK293T cells[1].
PROTAC α-synuclein degrader 5 (10 μM; 24 h) reduces the level of reactive oxygen species (ROS) in PFF-treated SH-SY5Y cells, restores mitochondrial membrane potential, and alleviates aggregate-induced cellular damage[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Snca OE-PFF seeding HEK293T cells
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Concentration:0.625, 1.25, 2.5, 5, 10, 20, 40 μM (48 h)
10 μM (0-48 h) -
Incubation Time:48 h
0, 3, 6, 12, 24, 48 h -
Result:Degraded α-synuclein aggregates in the Snca OE-PFF seeding model HEK293T cells, with a DC50 of 7.51 μM and a Dmax of 89%. It exhibits high selectivity for aggregated α-synuclein and does not affect the level of α-synuclein monomers.
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Cell Line:Snca OE-PFF seeding HEK293T cells
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Concentration:10 μM
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Incubation Time:48 h
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Result:Achieved the degradation of α-synuclein aggregates in the Snca OE-PFF seeding model HEK293T cells via the combined action of the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway (ALP); after treatment with MG132 (HY-13259), BafA1 (HY-100558) or LC3B knockdown, the degradation efficiency decreased significantly.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NL5901 (pkls2386 [unc-54p::αSyn::YFP])[1]
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Dosage:20 μM; 40 μM; 80 μM
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Administration:incubated in liquid NGM culture medium; 48 hours
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Result:Degraded αSyn aggregates in a dose-dependent manner.
Reduced the total number of αSyn-YFP fluorescent punctae with increasing concentrations.
Reduced the mean fluorescence intensity (MFI) of αSyn-YFP with increasing concentrations.
Chemical Information
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CAS No. 2781922-42-5
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Appearance Solid
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Molecular Weight 767.78
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Formula C39H41N7O10
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Color Light yellow to yellow
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SMILES
O=C(NCCOCCOCCOCCNC1=CC=CC(C(N2C3C(NC(CC3)=O)=O)=O)=C1C2=O)CNC4=CC(C5=CC(C6=CC7=C(C=C6)OCO7)=NN5)=CC=C4
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
-20°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 : ≥ 100 mg/mL (130.25 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
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: ≥ 3.75 mg/mL (4.88 mM); Clear solution
This protocol yields a clear solution of ≥ 3.75 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (37.5 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.
Purity & Documentation
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Data Sheet (281 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 | 1.3025 mL | 6.5123 mL | 13.0246 mL | 32.5614 mL |
| 5 mM | 0.2605 mL | 1.3025 mL | 2.6049 mL | 6.5123 mL | |
| 10 mM | 0.1302 mL | 0.6512 mL | 1.3025 mL | 3.2561 mL | |
| 15 mM | 0.0868 mL | 0.4342 mL | 0.8683 mL | 2.1708 mL | |
| 20 mM | 0.0651 mL | 0.3256 mL | 0.6512 mL | 1.6281 mL | |
| 25 mM | 0.0521 mL | 0.2605 mL | 0.5210 mL | 1.3025 mL | |
| 30 mM | 0.0434 mL | 0.2171 mL | 0.4342 mL | 1.0854 mL | |
| 40 mM | 0.0326 mL | 0.1628 mL | 0.3256 mL | 0.8140 mL | |
| 50 mM | 0.0260 mL | 0.1302 mL | 0.2605 mL | 0.6512 mL | |
| 60 mM | 0.0217 mL | 0.1085 mL | 0.2171 mL | 0.5427 mL | |
| 80 mM | 0.0163 mL | 0.0814 mL | 0.1628 mL | 0.4070 mL | |
| 100 mM | 0.0130 mL | 0.0651 mL | 0.1302 mL | 0.3256 mL |
PROTAC α-synuclein degrader 5 Related Classifications
HY-155021 Related Classifications
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Keywords
- PROTAC α-synuclein degrader 5
- 2781922-42-5
- PROTACs
- α-synuclein
- Reactive Oxygen Species (ROS)
- Autophagy
- autophagy-lysosome pathway
- E3 ligase CRBN
- ubiquitination
- C. elegans NL5901
- ROS
- Caenorhabditis elegans
- neuroblastoma cells
- α-synuclein aggregates
- synucleinopathies
- mitochondrial membrane potential
- Inhibitor
- inhibitor
- inhibit