PROTAC STING degrader-4
Based on 1 Customer Validation
PROTAC STING degrader-4 is a nitro-free covalent STING PROTAC degrader with a DC50 of 3.23 μM. PROTAC STING degrader-4 effectively inhibits STING as well as its downstream signaling, such as p-TBK1 and p-NF-κB (p-P65), and immune-inflammatory cytokines. PROTAC STING degrader-4 mitigates kidney and blood inflammation in Cisplatin (HY-17394)-induced acute kidney injury (AKI) mice model.
(Pink: STING ligand (HY-176183); Blue: Cereblon ligand (HY-103596); Black: linker (HY-176182)).
For research use only. We do not sell to patients.
- Purity: 98.96%
- Formula: C39H42Cl2N8O9
- Molecular Weight:837.70
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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
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Biological Activity
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NF-κB |
TBK1 |
PROTAC STING degrader-4 (Compound 2h) (0.6-40 μM, 2-72 h) dose- and time- dependently degrades STING for 72 h, with a DC50 of 3.23 μM (24 h) in THP-1 dual cells[1].
PROTAC STING degrader-4 (10 μM, 48 h) induces the degradation of STING via the proteasome pathway[1].
PROTAC STING degrader-4 (0.3-20 μM, 16 h) dose-dependently reduced protein levels of p-TBK1 and p-NF-κB (p-P65), suppressing the STING downstream signaling cascade beyond direct degradation of STING in THP1-Dual cells[1].
PROTAC STING degrader-4 (0.6-20 μM, 2 h) significantly and dose-dependently decreases the production of IFN-β and CXCL10 and inhibits IFNB1, CXCL10 and ISG15 mRNA expression in THP1-Dual cells induced by MSA-2 (HY-136927)[1].
PROTAC STING degrader-4 (0.03-30 μM, 24-48 h) exhibits a no or weak cytotoxicity in THP1-Dual and RAW-Lucia cells (below 20 μM) and in human and mouse normal cells (below 30 μM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:THP-1 dual cells
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Concentration:0.6, 1.2, 2.5, 5, 10, 20, 40 μM
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Incubation Time:2, 4, 8, 12, 24, 48, 72 h
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Result:Dose-dependently degraded STING with a DC50 of 3.23 μM (24 h) in THP-1 dual cells.
Continuously reduced the expression level of STING in THP1-dual cells for 72 h in THP-1 dual cells.
Induced potent degradation of STING, and this degradation effect was not inhibited by lysosome inhibitor BAF (Bafilomycin A1) (HY-100558) but was reversed by proteasome inhibitor MG132 (HY-13259) Induced the degradation of STING via the proteasome pathway rather than its warhead molecule or E3 ligase ligand, BAF (a lysosome inhibitor) and MG132 (a proteasome inhibitor).
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Cell Line:THP-1 dual cells
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Concentration:0.3, 0.6, 1.25, 2.5, 5, 10, 20 μM
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Incubation Time:2 h following MSA-2 (10 μM) for 16 h
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Result:Dose-dependently reduced protein levels of p-TBK1 and p-NF-κB (p-p65), suppressing the STING downstream signaling cascade beyond direct degradation of STING.
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Cell Line:THP-1 dual cells
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Concentration:0.6, 1.25, 2.5, 5, 10, 20 μM
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Incubation Time:2 h following MSA-2 (10 μM) for 24 h
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Result:Significantly and dose-dependently inhibited IFNB1, CXCL10 and ISG15 mRNA expression in THP1-Dual cells.
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Cell Line:THP1-Dual, RAW-Lucia cells, human normal cell lines (HEK293T and WI38VA-13) and mouse normal cell lines (HT22 and MEF).
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Concentration:0.03, 0.07, 0.15, 0.31, 0.62, 1.25, 2.5, 5, 10, 20 μM (THP1-Dual and RAW-Lucia cells), 1.1, 3.3, 10, 30 μM (four human and mouse normal cell lines)
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Incubation Time:24, 48 h
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Result:Did not exhibit significant inhibition of cellular viability below 20 μM in THP1-Dual and RAW-Lucia cells.
Exhibited no or weak cytotoxicity against four human and mouse cell lines at concentrations below 30 μM.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male C57BL/6 mice (8 weeks old) were given Cisplatin administration (15 mg/kg) 1 h after PROTAC STING degrader-4 to induce AKI mice model[1].
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Dosage:30 mg/kg
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Administration:i.p., daily for 3 days and then collected blood and kidney samples after cisplatin induction1.
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Result:Potently mitigated ischemic symptoms of kidneys.
Significantly reduced the protein level of STING and p-IRF3 in kidney tissues.
Effectively reduced the mRNA levels of Tnfα, Isg15 and Cxcl10.
Effectively suppressed the production of CXCL10, IFN-β, IL-6 in plasma.
Chemical Information
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Appearance Solid
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Molecular Weight 837.70
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Formula C39H42Cl2N8O9
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Color Light yellow to light brown
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SMILES
ClC(C=C(C=N1)NC(NC2=CNC3=CC=C(C=C32)Cl)=O)=C1N(CC4)CCN4CCOCCOCCOCCOC5=C6C(N(C(C6=CC=C5)=O)C7CCC(NC7=O)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
DMSO : 100 mg/mL (119.37 mM; Need ultrasonic; 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. 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. 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)
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.
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.
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 (275 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. 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 |
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| DMSO | 1 mM | 1.1937 mL | 5.9687 mL | 11.9374 mL | 29.8436 mL |
| 5 mM | 0.2387 mL | 1.1937 mL | 2.3875 mL | 5.9687 mL | |
| 10 mM | 0.1194 mL | 0.5969 mL | 1.1937 mL | 2.9844 mL | |
| 15 mM | 0.0796 mL | 0.3979 mL | 0.7958 mL | 1.9896 mL | |
| 20 mM | 0.0597 mL | 0.2984 mL | 0.5969 mL | 1.4922 mL | |
| 25 mM | 0.0477 mL | 0.2387 mL | 0.4775 mL | 1.1937 mL | |
| 30 mM | 0.0398 mL | 0.1990 mL | 0.3979 mL | 0.9948 mL | |
| 40 mM | 0.0298 mL | 0.1492 mL | 0.2984 mL | 0.7461 mL | |
| 50 mM | 0.0239 mL | 0.1194 mL | 0.2387 mL | 0.5969 mL | |
| 60 mM | 0.0199 mL | 0.0995 mL | 0.1990 mL | 0.4974 mL | |
| 80 mM | 0.0149 mL | 0.0746 mL | 0.1492 mL | 0.3730 mL | |
| 100 mM | 0.0119 mL | 0.0597 mL | 0.1194 mL | 0.2984 mL |
PROTAC STING degrader-4 Related Classifications
HY-176180 Related Classifications
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