Keap1-p-p62-IN-1
Keap1-p-p62-IN-1 is a potent and selective Keap1-p-p62 inhibitor with an IC50 of 0.11 μM. Keap1-p-p62-IN-1 shows 18.73-fold selectivity over Keap1-Nrf2 interaction. Keap1-p-p62-IN-1 normalizes Nrf2 ubiquitination, sensitizes cells to Sorafenib (HY-10201)-induced ferroptosis. Keap1-p-p62-IN-1 can be used for the research of p62 aberrant hepatocellular carcinoma.
For research use only. We do not sell to patients.
- Formula: C33H35N5O5S
- Molecular Weight:613.73
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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
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Keap1-p-p62-IN-1 (compound 13) (0.625-5 μM; 48 h) induces ferroptosis in p62-aberrant Huh-1 HCC cells in a Keap1-dependent manner, as evidenced by concentration-dependent downregulation of ferroptosis-related proteins/genes, GSH depletion, iron overload, and increased lipid peroxidation (MDA, 4-HNE, Liperfluo)[1].
Keap1-p-p62-IN-1 (0.03-5 μM; 24-72 h) selectively disrupts Keap1-p-p62 PPI in a dose- and time-dependent manner, causing increased Nrf2 ubiquitination in HEK293T and Huh-1 cells[1].
Keap1-p-p62-IN-1 (0.625-5 μM; 24-72 h) specifically inhibits Nrf2 activity in tumor
cells (Huh-1; Huh-7; AML 12; A549) with p62-dependent overactivation of Nrf2[1].
Keap1-p-p62-IN-1 (1.25-10 μM; 48 h) induces ferroptosis in specific HCC cells[1].
Keap1-p-p62-IN-1 (1.25-10 μM; 14 days) dose-dependently inhibits colony formation in Huh-1 HCC cells[1].
Keap1-p-p62-IN-1 (1.25-10 μM; 24-72 h) selectively induces ferroptosis in Huh-1 HCC cells with p62-dependent overactivation of Nrf2[1].
Keap1-p-p62-IN-1 (2.5-10 μM; 24 h-14 days)sensitizes Huh-1 cells bearing p62-mediated Nrf2 hyper-activation to Sorafenib by cooperatively inducing ferroptosis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK293T, Huh-1 cells
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Concentration:0.03; 0.1; 0.3 μM (HEK293T), 2.5; 5 μM (Huh-1 cells)
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Incubation Time:24; 36; 48; 72 h
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Result:Effectively interfered with the Keap1−p-p62 interaction in a concentration-dependent manner without affecting the Keap1-Nrf2 interaction.
Barely disrupted the binding of both ETGE and DLGex motifs to Keap1.
Recovered the ability of Keap1 to interact with Nrf2 because of the elevated level of p62-free Keap1, leading to a decrease in the Nrf2 protein level of total cell lysate.
Elevated the accumulation of ubiquitinated Nrf2 upon MG132 (HY-13259) treatment.
Caused a time-dependent reduction in Nrf2 protein in both the nucleus and cytoplasm.
Showed a remarkable upregulation of the protein level of Keap1.
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Cell Line:Huh-1 cells
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Concentration:2.5; 5 μM
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Incubation Time:24; 36; 48; 72 h
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Result:Had no significant effect on the transcription level of NFE2L2 (encoding Nrf2 protein) in Huh-1 cells.
Concentration-dependently reduced mRNA levels of SLC7A11, FTL, and GPX4.
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Cell Line:Huh-1; Huh-7; AML 12; A549
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Concentration:0.625; 1.25; 2.5; 5 μM
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Incubation Time:24; 36; 48; 72 h
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Result:Decreased the protein levels of Nrf2 and its downstream genes in a concentration- and time-dependent manner, including gluta-
mate-cysteine ligase catalytic subunit (GCLC), NAD(P)H dehydrogenase (quinone) 1 (NQO1), and heme oxygenase-1 (HO-1).
Downregulate the protein levels of these ferroptosis-related genes in a concentration-dependent manner.
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Cell Line:Huh-1; Huh-7; AML 12; A549
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Concentration:0.625; 1.25; 2.5; 5 μM
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Incubation Time:24; 36; 48; 72 h
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Result:Significantly downregulated the
mRNA levels of Nrf2-regulated genes GCLC, NQO1, and HO-1, with IC50 values of 4.62 μM, 4.24 μM, and 3.51 μM, respectively.
Induced a time-dependent decrease in the mRNA expression of GCLC, NQO1, and HO-1.
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Cell Line:Huh-1 HCC cells
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Concentration:1.25; 2.5; 5; 10 μM
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Incubation Time:48 h
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Result:Decreased cell viability in a dose-dependent manner.
The growth inhibition induced by 13 in Huh-1 cells was mitigated by Fer-1 (5 μM).
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Cell Line:Huh-1 HCC cells
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Concentration:1.25; 2.5; 5; 10 μM
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Incubation Time:14 days
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Result:Inhibited colony formation of Huh-1 HCC cells in a dose-dependent manner.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice (female) subcutaneously inoculated with Huh-1 cells[1]
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Dosage:20; 40 mg/kg
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Administration:i.p.; daily; 28 days
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Result:Achieved a tumor growth inhibition (TGI) rate of 11.1% at 20 mg/kg.
Achieved a TGI of 30.1% at 40 mg/kg.
Decreased protein levels of Nrf2, glutamate-cysteine ligase catalytic subunit (GCLC), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in tumor tissues.
Reduced glutathione (GSH) levels in tumor tissues.
Increased ferrous iron (Fe2+) levels in tumor tissues.
Increased malondialdehyde (MDA) levels in tumor tissues.
Caused no significant body weight loss or histopathological lesions in major organs.
Chemical Information
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Molecular Weight 613.73
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Formula C33H35N5O5S
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SMILES
CC1=CC(C)=C(S(N(C2=C(C=CC=C3)C3=C(OC(C4=CC=C(C(C)(C)C)C=C4)C(O)=O)C=C2)CC5=NN=NN5)(=O)=O)C(C)=C1
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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)
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