PROTAC cGAS degrader-1
Based on 1 Customer Validation
PROTAC cGAS degrader-1 is a potent and selective cGAS PROTAC degrader, with DC50 values of 0.9 μM and 4.6 μM in THP-1 and RAW 264.7 cells, respectively. PROTAC cGAS degrader-1 induces proteasome-mediated degradation of cGAS, inhibits the cGAS signaling pathway, and attenuates double-stranded DNA-induced activation of cGAS in human and mouse cells. PROTAC cGAS degrader-1 is applicable to research related to ulcerative colitis.
(Pink: cGAS ligand (HY-133916); Blue: Cereblon ligand (HY-43722); Black: linker (HY-W411604)).
For research use only. We do not sell to patients.
- Purity: 99.07%
- CAS No.: 3118499-89-8
- Formula: C36H33Cl2N7O5
- Molecular Weight:714.60
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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
PROTAC cGAS degrader-1 (TH35) potently degrades cGAS in human THP-1 cells with a DC50 of 0.9 μM and achieves 94.4% maximum degradation[1].
PROTAC cGAS degrader-1 potently degrades cGAS in murine RAW 264.7 cells with a DC50 of 4.6 μM and achieves 91.6% maximum degradation[1].
PROTAC cGAS degrader-1 (10 μM; 1-24 h) induces time-dependent cGAS degradation in human THP-1 cells, with significant degradation detected at 8 h and further increases at 12 and 24 h of treatment[1].
PROTAC cGAS degrader-1 (10 μM; 48 h treatment with 2 h pretreatment) induces cGAS degradation in human THP-1 cells via a CRBN-dependent ubiquitin-proteasome pathway[1].
PROTAC cGAS degrader-1 potently inhibits HT-DNA-induced cGAS signaling in human THP1-Lucia ISG cells with an IC50 of 1.8 μM[1].
PROTAC cGAS degrader-1 potently inhibits HT-DNA-induced cGAS signaling in murine RAW-Lucia ISG cells with an IC50 of 4.8 μM[1].
PROTAC cGAS degrader-1 (5.0-20.0 μM; 36 h preincubation followed by 6 h HT-DNA transfection) dose-dependently reduces HT-DNA-induced cGAMP production in human THP-1 cells[1].
PROTAC cGAS degrader-1 (1.25-10.0 μM; 12 h preincubation followed by 8 h HT-DNA stimulation) dose-dependently inhibits HT-DNA-induced IFNB and CXCL10 mRNA expression in human THP-1 cells[1].
PROTAC cGAS degrader-1 (2.5-20.0 μM; 12 h preincubation followed by 8 h HT-DNA stimulation) dose-dependently inhibits HT-DNA-induced Ifnb and Cxcl10 mRNA expression in murine RAW 264.7 cells[1].
PROTAC cGAS degrader-1 (5.0-20.0 μM; 24 h) significantly inhibits basal Ifnb mRNA expression in Trex1−/− murine RAW 264.7 cells[1].
PROTAC cGAS degrader-1 (0.24-60.0 μM; 48 h) exhibits low in vitro cytotoxicity, with no significant cell viability reduction at concentrations up to 60 μM in THP-1, RAW 264.7, THP1-Lucia ISG, and RAW-Lucia ISG cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human THP-1 cells
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Concentration:10 μM
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Incubation Time:1 h, 2 h, 4 h, 6 h, 8 h, 12 h,24 h
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Result:Induced time-dependent degradation of cGAS, with significant degradation observed starting at 8 h, and increasing degradation at 12 h and 24 h.
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Cell Line:human THP-1 cells
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Concentration:10 μM
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Incubation Time:48 h
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Result:Induced cGAS degradation that was completely abrogated by pretreatment with G140, Lenalidomide, or MG132.
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Cell Line:human THP-1 cells
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Concentration:1.25 μM, 2.5 μM, 5 μM, 10.0 μM
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Incubation Time:12 h (preincubation); 8 h (HT-DNA stimulation post-preincubation)
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Result:Dose-dependently suppressed HT-DNA-induced IFNB and CXCL10 mRNA expression.
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Cell Line:Trex1-/- murine RAW 264.7 cells
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Concentration:5.0-20.0 μM
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Incubation Time:24 h
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Result:Significantly reduced basal Ifnb mRNA levels.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male, 8-12 weeks old, 20-25 g, DSS-induced ulcerative colitis)[1]
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Dosage:20 mg/kg; 50 mg/kg
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Administration:i.p.; once daily; day 4 of DSS administration to day 11
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Result:Significantly alleviated DSS-induced weight loss, reduced Disease Activity Index (DAI) scores, increased colon length, normalized spleen weight, and lowered colonic histopathological scores compared to the DSS-only group.
Induced a significant, dose-dependent reduction in colonic cGAS protein levels, and blocked phosphorylation of downstream cGAS signaling pathway components (STING, TBK1, IRF3).
Significantly inhibited colonic mRNA expression of IFNB, Tnf-α, and IL-6 in a dose-dependent manner.
Significantly reduced serum TNF-α and IL-6 concentrations.
Significantly reduced colonic citrullinated histone H3 (citH3) levels and immunofluorescence signal, indicating inhibition of neutrophil extracellular trap (NET) formation.
Chemical Information
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CAS No. 3118499-89-8
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Appearance Solid
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Molecular Weight 714.60
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Formula C36H33Cl2N7O5
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Color White to off-white
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SMILES
ClC1=CC(C2=NN(C=C2)C)=C3C(NC4=C3CN(CC4)C(CNC(CCCC#CC5=C(C6=CC=C5)CN(C6=O)C7CCC(NC7=O)=O)=O)=O)=C1Cl
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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 (139.94 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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (3.50 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
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 (280 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.3994 mL | 6.9969 mL | 13.9938 mL | 34.9846 mL |
| 5 mM | 0.2799 mL | 1.3994 mL | 2.7988 mL | 6.9969 mL | |
| 10 mM | 0.1399 mL | 0.6997 mL | 1.3994 mL | 3.4985 mL | |
| 15 mM | 0.0933 mL | 0.4665 mL | 0.9329 mL | 2.3323 mL | |
| 20 mM | 0.0700 mL | 0.3498 mL | 0.6997 mL | 1.7492 mL | |
| 25 mM | 0.0560 mL | 0.2799 mL | 0.5598 mL | 1.3994 mL | |
| 30 mM | 0.0466 mL | 0.2332 mL | 0.4665 mL | 1.1662 mL | |
| 40 mM | 0.0350 mL | 0.1749 mL | 0.3498 mL | 0.8746 mL | |
| 50 mM | 0.0280 mL | 0.1399 mL | 0.2799 mL | 0.6997 mL | |
| 60 mM | 0.0233 mL | 0.1166 mL | 0.2332 mL | 0.5831 mL | |
| 80 mM | 0.0175 mL | 0.0875 mL | 0.1749 mL | 0.4373 mL | |
| 100 mM | 0.0140 mL | 0.0700 mL | 0.1399 mL | 0.3498 mL |
PROTAC cGAS degrader-1 Related Classifications
HY-172208 Related Classifications
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