SG16
SG16 (Keap1-Nrf2-IN-28) is an orally active Keap1-Nrf2 inhibitor. SG16 disrupts the binding of Keap1 to Nrf2, promotes the nuclear translocation of Nrf2, upregulates the downstream antioxidant proteins HO-1 and GCLM, and simultaneously inhibits microglial overactivation and proinflammatory cytokine secretion. By activating the Nrf2 pathway, SG16 can be used in studies on oxidative stress, ischemic stroke and acute liver injury.
For research use only. We do not sell to patients.
- CAS No.: 3075750-60-3
- Formula: C22H16FNO5S
- Molecular Weight:425.43
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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]|
Nrf2 |
In Vitro
SG16 (5-10 μM; 6 h LPS (HY-D1056), with 1 h pretreatment) activates the Nrf2 antioxidant pathway in LPS-stimulated BV2 mouse microglial cell line by upregulating Nrf2, HO-1 and GCLM at the protein level[1].
SG16 (Keap1-Nrf2-IN-28) (1-500 μM; 12-24 h) shows no significant cytotoxicity against the BV2 mouse microglial cell line at concentrations up to 10 μM after 12 h or 24 h of incubation, while concentrations ≥50 μM induce significant cytotoxicity at 24 h[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:BV2 mouse microglial cell line
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Concentration:1 μM; 10 μM; 20 μM; 50 μM; 100 μM; 200 μM; 500 μM
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Incubation Time:12 h; 24 h
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Result:Exhibited negligible cytotoxicity at 1-10 μM after 12 h and 24 h incubation.
Showed a slight decrease in cell viability at 20 μM after 24 h.
Induced significant cytotoxicity at 50-500 μM after 24 h.
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Cell Line:LPS-stimulated BV2 mouse microglial cell line
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Concentration:5 μM; 10 μM
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Incubation Time:6 h (with 1 h pretreatment)
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Result:Significantly reduced the mRNA expression levels of pro-inflammatory factors IL-6, IL-1β, and TNF-α at 10 μM, with greater efficacy than 5 μM.
Significantly upregulated the mRNA expression of antioxidant genes HO-1 and GCLM at 10 μM.
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Cell Line:LPS-stimulated BV2 mouse microglial cell line
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Concentration:5 μM; 10 μM
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Incubation Time:6 h (with 1 h pretreatment)
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Result:Further enhanced LPS-induced Nrf2 protein expression at 10 μM.
Induced significant increases in HO-1 and GCLM protein expression at 10 μM.
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Cell Line:AML12
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Concentration:0.5 μM, 2.5 μM, 5 μM, 10 μM
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Incubation Time:16 h
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Result:Induced a 10.7-fold increase in HO-1 mRNA expression at 10 μM.
Upregulated GCLM mRNA and Akr1c1 mRNA.
Increased HO-1, GCLM, and Akr1c1 mRNA levels gradually across 0.5 μM to 10 μM, with statistically significant increases (P < 0.05 at 0.5 μM, P < 0.01 at 2.5, 5, 10 μM) relative to untreated controls.
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Cell Line:AML12
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Concentration:0.5 μM, 2.5 μM, 5 μM, 10 μM
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Incubation Time:16 h
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Result:Upregulated protein levels of Nrf2, HO-1, and GCLM dose-dependently in AML12 cells.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male, 21-22 g, middle cerebral artery occlusion for 45 minutes followed by 24 hours of reperfusion)[1]
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Dosage:6.25 mg/kg; 12.5 mg/kg; 25 mg/kg
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Administration:i.p.; single dose at reperfusion onset
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Result:Significantly reduced neurological deficit scores, shortened forelimb tape contact time, and reduced cerebral infarct volume (12.5 mg/kg).
Significantly reduced cerebral infarct volume (25 mg/kg).
Attenuated neuronal loss in the ischemic cortex, as shown by increased relative mean fluorescence intensity of NeuN and increased Nissl-positive cell density (12.5 mg/kg).
Reduced microglial activation (decreased relative mean fluorescence intensity of Iba-1) and suppressed MCAO/R-induced upregulation of IL-6, IL-1β, and TNF-α mRNA levels in ischemic brain tissue (12.5 mg/kg).
Reduced malondialdehyde (MDA) levels and prevented depletion of superoxide dismutase (SOD) activity in ischemic brain tissue (12.5 mg/kg).
Increased Nrf2, HO-1, and GCLM protein expression (measured as actin ratio) in ischemic brain tissue (12.5 mg/kg).
Abrogated improvements in neurological deficit scores, cerebral infarct volume, and tape removal test performance, and reversed upregulation of Nrf2, HO-1, and GCLM protein expression when co-administered with Nrf2 inhibitor ML385.
Was detected in ischemic brain tissue at 3, 6, 12, and 24 hours post-administration, with concentrations declining over time but remaining quantifiable at 24 hours.
Caused no pathological damage to heart, kidney, liver, lung, or spleen tissue, as assessed by HE staining.
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Animal Model:C57BL/6 (male, 8-10 weeks old, APAP-induced acute liver injury model)[2]
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Dosage:12.5 mg/kg; 25 mg/kg
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Administration:i.p.; single dose
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Result:Achieved dose-dependent systemic exposure, with plasma concentrations of 50 ng/mL (12.5 mg/kg dose) and 155 ng/mL (25 mg/kg dose), and liver tissue concentrations of 175 ng/g (12.5 mg/kg dose) and 485 ng/g (25 mg/kg dose).
Induced a 100-fold upregulation of HO-1 mRNA in liver tissue at the 25 mg/kg dose, and dose-dependently increased GCLM mRNA levels.
Promoted Nrf2 nuclear translocation, dose-dependently disrupted Keap1-Nrf2 binding, and dose-dependently reduced serum ALT, AST, NO, IL-6, and TNFα levels, while restoring serum CAT activity.
Reduced liver tissue damage, cell apoptosis, neutrophil invasion (MPO-positive cells), and macrophage aggregation (F4/80-positive cells) in a dose-dependent manner.
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Animal Model:C57BL/6 Nrf2 knockout (male, 8-10 weeks old, APAP-induced acute liver injury model)[2]
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Dosage:25 mg/kg
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Administration:i.p.; single dose
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Result:Had no significant effect on serum ALT and AST levels in Nrf2 knockout mice.
Failed to reduce liver tissue damage, cell apoptosis, neutrophil invasion (MPO-positive cells), or macrophage aggregation (F4/80-positive cells) compared to APAP-only treated Nrf2 knockout mice.
Chemical Information
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CAS No. 3075750-60-3
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Molecular Weight 425.43
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Formula C22H16FNO5S
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SMILES
O=S(C1=CC=C(F)C=C1)(NC2=CC3=C(C=C2)C(C=C(C4=CC=C(OC)C=C4)O3)=O)=O
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Synonyms
Keap1-Nrf2-IN-28
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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
[1]. Li S, et al. Sulfonamide-flavonoid analogue SG16 shows promise as a novel anti-inflammatory agent for ischemic stroke treatment. Bioorganic chemistry. 2026 Jun 18;180:110137. [Content Brief]
[2]. Sang Y, et al. Fluorinated sulfonamide-flavonoid derivatives as novel Keap1-Nrf2 inhibitors: Potent induction of cytoprotective gene HO-1 in vivo. Eur J Med Chem. 2025 Jul 5;291:117650. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SG16 Related Classifications
HY-172598 Related Classifications
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