Art. -Nr.: HY-172208

PROTAC cGAS degrader-1

Name: PROTAC cGAS degrader-1
Brand: MedChemExpress
SKU: HY-172208
Price: 640.00 USD
Availability: InStock
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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)).

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Reinheit : 99.07%
CAS. Nr.: 3118499-89-8
Formel: C₃₆H₃₃Cl₂N₇O₅
Molecular Weight:714.60

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

PROTAC cGAS degrader-1 Chemical Structure

CAS. Nr.: 3118499-89-8

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Use of MCE Products

Fluorescent Dye

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

Biologische Aktivität
- Beschreibung
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Protokoll (2)
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

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^[1]. (Pink: cGAS ligand (HY-133916); Blue: Cereblon ligand (HY-43722); Black: linker (HY-W411604)).

Alle PROTACs Isoform-spezifische Produkte anzeigen :

In Vitro

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. Further protocols information, click here.

Western Blot Analysis^[1]

View Protocol

Cell Line:

human THP-1 cells
Concentration:

10 μM
Incubation Time:

1 h, 2 h, 4 h, 6 h, 8 h, 12 h,24 h
Result:

Induced time-dependent degradation of cGAS, with significant degradation observed starting at 8 h, and increasing degradation at 12 h and 24 h.

Western Blot Analysis^[1]

View Protocol

Cell Line:

human THP-1 cells
Concentration:

10 μM
Incubation Time:

48 h
Result:

Induced cGAS degradation that was completely abrogated by pretreatment with G140, Lenalidomide, or MG132.

Real Time qPCR^[1]

View Protocol

Cell Line:

human THP-1 cells
Concentration:

1.25 μM, 2.5 μM, 5 μM, 10.0 μM
Incubation Time:

12 h (preincubation); 8 h (HT-DNA stimulation post-preincubation)
Result:

Dose-dependently suppressed HT-DNA-induced IFNB and CXCL10 mRNA expression.

Real Time qPCR^[1]

View Protocol

Cell Line:

Trex1^-/^- murine RAW 264.7 cells
Concentration:

5.0-20.0 μM
Incubation Time:

24 h
Result:

Significantly reduced basal Ifnb mRNA levels.

Parmacokinetics

Species	Dose	Route	C_max	AUC_0-24	AUC_0-∞	V_d	CL	MRT_0-t	T_1/2
Mice^[1]	1.0 mg/kg	i.v.	1608.6 μg/L	529.9 μg/L·h	530.6 μg/L·h	8.1 L/kg	1.9 L/h/kg	0.9 h	3.0 h
Mice^[1]	20.0 mg/kg	i.p.	248.0 μg/L	2022.9 μg/L·h	2797.4 μg/L·h	/	/	7.9 h	13.7 h

In Vivo

PROTAC cGAS degrader-1 (TH35) (20-50 mg/kg; i.p.; once daily; day 4 of DSS administration to day 11) dose-dependently ameliorates DSS (HY-116282C)-induced ulcerative colitis in C57BL/6 mice by degrading colonic cGAS, blocking downstream cGAS-STING signaling, reducing pro-inflammatory cytokine production, and inhibiting NET formation^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

C57BL/6 (male, 8-12 weeks old, 20-25 g, DSS-induced ulcerative colitis)^[1]
Dosage:

20 mg/kg; 50 mg/kg
Administration:

i.p.; once daily; day 4 of DSS administration to day 11
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

CAS. Nr. 3118499-89-8
Appearance Solid
Molecular Weight 714.60
Formel C₃₆H₃₃Cl₂N₇O₅
Color White to off-white
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
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Lösungsmittel & Löslichkeit

In Vitro:

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.3994 mL

6.9969 mL

13.9938 mL

5 mM

0.2799 mL

1.3994 mL

2.7988 mL

10 mM

0.1399 mL

0.6997 mL

1.3994 mL

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.

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)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

Protocol 1

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.

Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (3.50 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Protokoll

All Animals and Diseases

DSS-Induced Colitis
Dextran sulfate sodium (DSS)-induced colitis is generated by administering DSS in mouse drinking water, producing epithelial injury, barrier disruption, weight loss, diarrhea, fecal blood, colon shortening, histologic mucosal damage, and inflammatory mediator changes; the model is mainly used to study acute or chronic intestinal inflammation resembling selected features of ulcerative colitis. DSS injury is interpreted through clinical and tissue readouts rather than a single molecular endpoint: daily body weight, stool consistency, and bleeding are combined into a disease activity index, while colon length, histology, cytokines, myeloperoxidase activity, intestinal permeability, and tight-junction markers provide complementary measures of inflammation and barrier damage.
TNBS-Induced Colitis
TNBS-induced colitis is produced by intrarectal delivery of 2,4,6-trinitrobenzene sulfonic acid in ethanol, where ethanol disrupts the mucosal barrier and TNBS haptenates colonic proteins, generating immune-mediated colonic inflammation with weight loss, diarrhea, ulceration, transmural injury, inflammatory-cell infiltration, and cytokine responses. The model is used as an experimental intestinal inflammation model with Crohn’s disease–like features, especially when Th1-type responses, IL-12–dependent inflammation, chronic relapsing inflammation, or fibrosis-related endpoints are studied.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (280 KB)
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)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. He P, et al. Discovery of a Novel CRBN-Recruiting cGAS PROTAC Degrader for the Treatment of Ulcerative Colitis. J Med Chem. 2025;68(5):5551-5572. [Content Brief]

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.

Complete Stock Solution Preparation Table

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

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PROTAC cGAS degrader-1

Alle PROTACs Isoform-spezifische Produkte anzeigen