PROTAC cGAS degrader-1

Name: PROTAC cGAS degrader-1
Brand: MedChemExpress
SKU: HY-172208
Rating: 4.5 (1 reviews)

Cat. No.: HY-172208 Purity: 99.07%: Data Sheet
COA

SDS
Handling Instructions
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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)).

For research use only. We do not sell to patients.

PROTAC cGAS degrader-1 Chemical Structure

CAS No. : 3118499-89-8

Size	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	In-stock	Estimated Time of Arrival: December 31
Solid
1 mg	In-stock	Estimated Time of Arrival: December 31
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	Get quote
100 mg	Get quote

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Customer Review

Based on 1 publication(s) in Google Scholar

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Biological Activity
Purity & Documentation
References
Customer Review

Description

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)).

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.

Western Blot Analysis^[1]

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]

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]

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]

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.

Molecular Weight

714.60

Formula

C₃₆H₃₃Cl₂N₇O₅

CAS No.

3118499-89-8

Appearance

Solid

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

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

Solvent & Solubility

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)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

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

View the 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.

Molarity Calculator
Dilution Calculator

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

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

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.

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.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

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

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

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

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).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

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

Purity: 99.07%

Select Batch:

Data Sheet (280 KB) SDS (251 KB)

COA (250 KB) HNMR (150 KB) RP-HPLC (166 KB) LCMS (108 KB)

Handling Instructions (2659 KB)

References

[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]

Complete Stock Solution Preparation Table

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