cGAS/HDAC-IN-1
cGAS/HDAC-IN-1 is an orally active dual cGAS/HDAC inhibitor that exhibits potent inhibitory activity against human and mouse cGAS (IC50: 0.17 and 1.80 μM, respectively) and moderate activity against HDAC3 and HDAC6 (IC50: 1.2 and 0.4 μM, respectively). cGAS/HDAC-IN-1 directly suppresses cGAS activity and increases its acetylation levels via HDAC3 inhibition. cGAS/HDAC-IN-1 is effective in murine models of inflammatory bowel disease and Aicardi-Goutières syndrome, and can be used in research on cGAS-dependent disorders.
For research use only. We do not sell to patients.
- Formula: C27H35Cl2N5O3
- Molecular Weight:548.50
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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HDAC1 6.87 μM (IC50) |
HDAC3 1.2 μM (IC50) |
HDAC6 0.4 μM (IC50) |
cGAS/HDAC-IN-1 (compound 31h) (24h) exhibits potent cGAS inhibitory activity (IC50: 0.17 μM) and a high safety index (CC50 > 50 μM) in THP1-Dual cells[1].
cGAS/HDAC-IN-1 (5 μM) exhibits minimal inhibition (-4%) in STING-activated cells, indicating high selectivity for cGAS in THP1-Dual cells[1].
cGAS/HDAC-IN-1 is much less potent in the mouse RAW-Lucia ISG cells, compared to the potency in the human THP1-Dual cells[1].
cGAS/HDAC-IN-1 exhibits moderate inhibitory activity against HDAC1, HDAC3, and HDAC6, with IC50 values of 6.87 μM, 1.2 μM, and 0.4 μM, respectively[1].
cGAS/HDAC-IN-1 (1.95-31.25 μM, 300 s) binds to human cGAS (h-cGAS) with a KD value of 27.9 μM[1].
cGAS/HDAC-IN-1 (7 h) directly inhibits cGAS enzymatic activity, with an IC50 value of 821 nM[1].
cGAS/HDAC-IN-1 (5-50 μM; 24 h) inhibits the cGAS downstream signaling pathway in dose- and time-dependent manner in THP1-Dual cells[1].
cGAS/HDAC-IN-1 (5-20 μM, 3 h) dose-dependently suppresses the phosphorylation of STING and IRF3 in THP1-Dual cells[1].
cGAS/HDAC-IN-1 (1-5 μM, 24 h) dose-dependently reverses the robust upregulation of cGAS pathway target genes, including IFN-β, ISG15, ISG56, and CXCL10, induced by dsDNA challenge in THP1-Dual cells[1].
cGAS/HDAC-IN-1 (5-31.25 μM; 4 h) suppresses cGAS by acting both as an HDAC3 inhibitor to prevent its deacetylation and as a direct cGAS enzymatic inhibitor in THP1-Dual cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:THP1-Dual cells
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Concentration:1 μM; 5 μM
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Incubation Time:24 h
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Result:Reversed the robust upregulation of cGAS pathway target genes, including IFN-β, ISG15, ISG56, and CXCL10, induced by dsDNA challenge dose-dependently.
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Cell Line:THP1-Dual cells
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Concentration:20 μM
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Incubation Time:3 h
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Result:Elevated cGAS acetylation levels in THP-1 cells.
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Cell Line:THP1-Dual cells
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Concentration:5 μM; 10 μM; 20 μM
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Incubation Time:3 h
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Result:Enhanced acetylation of histones (H3) and tubulin, suggesting broad HDAC inhibition.
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Cell Line:THP1-Dual cells
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Concentration:5 μM; 10 μM; 20 μM
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Incubation Time:3 h
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Result:Enhanced acetylation of histones (H3) and tubulin, suggesting broad HDAC inhibition.
cGAS/HDAC-IN-1 (40 mg/kg; p.o.; once a day; 7 days) alleviates Aicardi-Goutières syndrome in the Trex1–/– mice model[1].
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 (7 weeks old) mice were pretreated with DSS for 7 days before administration of compound[1].
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Dosage:40 mg/kg; 60 mg/kg;
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Administration:p.o.; once a day; 10 days
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Result:Improved the shortening of colon length caused by ulcerative inflammation at both doses significantly.
Improved the infiltration of inflammatory cells, damage to epithelial cells, and destruction of crypts effectively.
Suppressed the mRNA expression of cGAS pathway-dependent cytokines and chemokines, including CXCL10, IL-6, TNF-α, and IL-1β significantly.
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Animal Model:Female C57BL/6 (5 weeks old) and C57BL/6 Trex1–/– mice (5 weeks old)[1].
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Dosage:40 mg/kg;
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Administration:p.o.; once a day; 7 days
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Result:Reduced serum IFN-β levels in AGS mice significantly.
Attenuated the serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK) significantly.
Reduced inflammatory levels.
Downregulated the mRNA expression of IFN-β, IL-6, CXCL10, and ISG15 in heart tissues significantly.
Suppressed the increased protein levels of type I IFN, IL-6, and CXCL10 largely.
Alleviated inflammation and tissue damage in the AGS mod effectively.
Chemical Information
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Molecular Weight 548.50
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Formula C27H35Cl2N5O3
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SMILES
ONC(CCCCCCCCCCC(N(C1)CCC2=C1C3=C(C4=NN(C)C=C4)C=C(Cl)C(Cl)=C3N2)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
cGAS/HDAC-IN-1 Related Classifications
HY-184398 Related Classifications
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