GSK3227634
GSK3227634 is a non-covalent inhibitor of the KEAP1-NRF2 protein-protein interaction. GSK3227634 binds to the Kelch domain of KEAP1, disrupts the KEAP1-NRF2 protein-protein interaction, and thereby activates the NRF2 antioxidant cytoprotective pathway. In a rat model of acute lung injury, intratracheal administration of GSK3227634 dose-dependently upregulates the expression of NRF2 downstream target genes such as NQO1, TXNRD1, and SRXN1, and elevates glutathione levels in lung tissue. GSK3227634 can be used for research on chronic obstructive pulmonary disease.
For research use only. We do not sell to patients.
- CAS No.: 1799977-30-2
- Formula: C29H33N5O5S
- Molecular Weight:563.67
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
NQO1 |
In Vitro
GSK3227634 binds tightly to the Kelch domain of KEAP1 with a pKd of 10.9, confirming reversible but very slow dissociation[1].
GSK3227634 binds to the KEAP1 complex with a pKdapp of 9.4 and exhibits dose-dependent competition against multiple proteins[1].
GSK3227634 potently binds KEAP1 in HepG2 cells with a pEC50 > 7.7 and exhibits dose-dependent stabilization of FABP1, YIPF3, and TUBB[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
GSK3227634 (0.3-10 μmol/kg; administered intratracheally at a dose volume of 67 μL/kg) shows target engagement and efficacy in a paraquat-induced rat model of pulmonary oxidative stress[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Han Wistar rats[1]
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Dosage:1, 10, 30, 100 μmol/kg
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Administration:i.v. infusion; over 6 h at 1.5 mL/h
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Result:In the lung, Increased NQO1 expression occurred in a dose-dependent manner from 1 to 100 μmol/kg upon GSK3227634 treatment, while expression levels of TXNRD1 and SRXN1 reached a maximum at 5 μmol/kg.
In the kidney, Elevated NQO1 expression achieved a maximal response at 10 μmol/kg, while the expression levels of TXNRD1 and SRXN1 reached a maximum at 5 μmol/kg.
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Animal Model:Lewis rats (Paraquat (0.05 mg/kg) was instilled into the trachea 24 h after GSK3227634 dosing)[1]
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Dosage:0.3, 1, 3, 10 μmol/kg
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Administration:i.t. administration in a dose volume of 67 μL/kg
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Result:Increased both NQO1 expression and protein levels in the lung occurred in a dose-dependent manner from 0.3 to 10 μmol/kg. This activated NRF2 pathway correlated well with a dose-dependent increase in total lung glutathione levels.
- RNA extraction experimental
- Pull-down
- Immunoprecipitation
- How to Select a Suitable Non-Mouse Animal Model
- Protocol for Bimolecular Fluorescence Complementation (BiFC) Assay
- Inhalation Toxicity Study
- Co-Immunoprecipitation
- Protocol for Yeast Two-Hybrid (Y2H) Assay
- How to Choose the Right Model Animal
Chemical Information
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CAS No. 1799977-30-2
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Molecular Weight 563.67
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Formula C29H33N5O5S
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SMILES
OC(C[C@@H](C1=CC(CN2C[C@@H](CC)OC(N=CC=C3)=C3S2(=O)=O)=C(C)C=C1)C4=C(C)C5=C(N(CC)N=N5)C=C4)=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)
GSK3227634 Related Classifications
HY-189367 Related Classifications
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Keywords
- GSK3227634
- 1799977-30-2
- GSK 3227634
- GSK-3227634
- Keap1-Nrf2
- Quinone Reductase
- rat kidney
- BEAS-2B cells
- human bronchial epithelial cells
- rat lung
- paraquat-induced lung oxidative stress
- NQO1
- NRF2
- KEAP1-NRF2 protein-protein interaction
- chronic obstructive pulmonary disease
- KEAP1 Kelch domain inhibitor
- Inhibitor
- inhibitor
- inhibit