2. NF-κB Metabolic Enzyme/Protease Apoptosis
  3. Keap1-Nrf2 Quinone Reductase Glutathione S-transferase Apoptosis TNF Receptor
  4. TBE 31

TBE 31 is an orally active Keap1/Nrf2 pathway activator and NQO1 inducer with a Dm value of 1.1 nM for NQO1. TBE 31 binds to cysteine residues of Keap1, inhibits ubiquitination and degradation of Nrf2, thereby activating the expression of ARE-dependent genes. TBE 31 induces cytoprotective enzymes including NQO1 and GST isoforms, promotes Nrf2 accumulation, and upregulates Nrf2-regulated genes related to antioxidation and lipid metabolism. TBE 31 inhibits pro-inflammatory responses, formation of AFB1-DNA adducts, endoplasmic reticulum stress, cell apoptosis (apoptosis), hepatic fibrosis, oxidative stress, and the expression of ChREBP. TBE 31 reduces the number of tumors in a mouse model of ultraviolet-induced skin carcinogenesis. TBE 31 enhances nerve growth factor-induced neurite outgrowth. TBE 31 attenuates LPS-induced serum TNF-α levels and immobility time in mice. TBE 31 can be used in research related to liver cancer, skin cancer, inflammation-related depression, and non-alcoholic steatohepatitis.

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TBE 31

TBE 31 Chemical Structure

CAS No. : 936475-62-6

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TBE 31 Related Antibodies

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Description

TBE 31 is an orally active Keap1/Nrf2 pathway activator and NQO1 inducer with a Dm value of 1.1 nM for NQO1. TBE 31 binds to cysteine residues of Keap1, inhibits ubiquitination and degradation of Nrf2, thereby activating the expression of ARE-dependent genes. TBE 31 induces cytoprotective enzymes including NQO1 and GST isoforms, promotes Nrf2 accumulation, and upregulates Nrf2-regulated genes related to antioxidation and lipid metabolism. TBE 31 inhibits pro-inflammatory responses, formation of AFB1-DNA adducts, endoplasmic reticulum stress, cell apoptosis (apoptosis), hepatic fibrosis, oxidative stress, and the expression of ChREBP. TBE 31 reduces the number of tumors in a mouse model of ultraviolet-induced skin carcinogenesis. TBE 31 enhances nerve growth factor-induced neurite outgrowth. TBE 31 attenuates LPS-induced serum TNF-α levels and immobility time in mice. TBE 31 can be used in research related to liver cancer, skin cancer, inflammation-related depression, and non-alcoholic steatohepatitis[1][2][3][4][5].

IC50 & Target[1]

NQO1

 

TNF-α

 

Cellular Effect
Cell Line Type Value Description References
Macrophage IC50
0.056 nM
Compound: (+/-)-31
Antiinflammatory activity in CD-1 mouse Macrophage assessed as inhibition of IFN-gamma induced NO production after 48 hrs by Griess reaction
Antiinflammatory activity in CD-1 mouse Macrophage assessed as inhibition of IFN-gamma induced NO production after 48 hrs by Griess reaction
[PMID: 21361338]
RAW IC50
1 nM
Compound: 4
Inhibition of interferon gamma-stimulated NO production in RAW 264.7 cells after 24 hrs
Inhibition of interferon gamma-stimulated NO production in RAW 264.7 cells after 24 hrs
[PMID: 17367124]
RAW264.7 IC50
1 nM
Compound: (+/-)-31
Antiinflammatory activity in mouse RAW264.7 cells assessed as inhibition of IFN-gamma induced NO production after 24 hrs by Griess reaction
Antiinflammatory activity in mouse RAW264.7 cells assessed as inhibition of IFN-gamma induced NO production after 24 hrs by Griess reaction
[PMID: 21361338]
RAW264.7 IC50
1 nM
Compound: 1, TBE-31
Inhibition of iNOS in LPS-stimulated mouse RAW264.7 cells assessed as inhibition of nitric oxide production after 48 hrs by Griess assay
Inhibition of iNOS in LPS-stimulated mouse RAW264.7 cells assessed as inhibition of nitric oxide production after 48 hrs by Griess assay
[PMID: 25965897]
RAW264.7 IC50
3 nM
Compound: (-)-31, enantiomer
Antiinflammatory activity in mouse RAW264.7 cells assessed as inhibition of IFN-gamma induced NO production after 24 hrs by Griess reaction
Antiinflammatory activity in mouse RAW264.7 cells assessed as inhibition of IFN-gamma induced NO production after 24 hrs by Griess reaction
[PMID: 21361338]
In Vitro

TBE 31 (48 h) potently induces NQO1 in Hepa1c1c7 cells, with a Dm value of 1.1 nM[1].
TBE 31 (0.25-1 μM; 24 h) potently induces ARE-dependent gene expression in AREc32 cells in a concentration-dependent manner in vitro[1].
TBE 31 (0.001-0.1 μM; 24 h) potently induces NQO1 in a concentration-dependent manner in wild-type MEF cells, and this induction depends on the transcription factor Nrf2[1].
TBE-31 binds reversibly to the thiol group in reduced dithiothreitol and the cysteine sensor of recombinant Keap1[2].
TBE-31 (0.001-0.1 µM; 4 days) enhances nerve growth factor-induced axonal outgrowth in PC12 cells in a concentration-dependent manner in vitro, reaching approximately 300% of the control level at the dose of 0.1 µM after 4 days of incubation[3].
TBE-31 (0.1 µM) upregulates Nrf2 protein levels and enhances nerve growth factor-induced axonal outgrowth in PC12 cells via an Nrf2-dependent mechanism[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

TBE 31 Related Antibodies
Parmacokinetics
Species Dose Route AUC0-24 T1/2 (Elimination)
Mice[2] 10 nmol/Kg p.o. 0.1955 nM·h/mL 10.2 h
In Vivo

TBE-31 (0.03-0.3 μM; topical administration; once every 24 hours; 3 consecutive doses) dose-dependently increases skin NQO1 activity up to 4.9-fold and GST activity up to 1.5-fold in healthy SKH-1 hairless mice[1].
TBE-31 (administered orally at 0.1-0.3 μM per 3 g of feed, once daily for 11 days) dose-dependently increases the activity and protein levels of cytoprotective enzymes by up to 5.0-fold in the liver, skin and stomach (but not the cerebral cortex) of healthy SKH-1 hairless mice, with no observed toxicity[1].
A single oral administration of TBE-31 (10 μM/kg) increases NQO1 activity by 2.4-fold in the liver and 1.5-fold in the heart of female C57BL/6 mice[2].
TBE-31 (40 nM per animal; topical administration; twice weekly; for approximately 30 weeks) significantly reduces the tumor number and burden in a UV-induced skin carcinogenesis mouse model with concurrent immunosuppression by Azathioprine (HY-B0256)[2].
TBE-31 (1-10 mg/kg; p.o.; single administration) exerts a dose-dependent anti-inflammatory effect on LPS (HY-D1056)-induced elevation of TNF-α, and significantly ameliorates LPS-induced depressive-like behaviors in mice at the dose of 10 mg/kg[3].
Treatment with TBE-31 (5 nM/g; p.o.; three times per week for 6 weeks) reverses diet-induced insulin resistance, alleviates hepatic steatosis, and improves non-alcoholic steatohepatitis (NASH) and liver fibrosis in diseased Nrf2+/+ mice; NAS is reduced by 40.8%, while glucose homeostasis, oxidative stress and inflammatory markers are all improved[4].
TBE-31 (5 nM/g; p.o.; three times per week; for 6 weeks) requires functional Nrf2 to improve insulin sensitivity, reduce hepatic steatosis, and alleviate non-alcoholic steatohepatitis (NASH) in mice with established diet-induced disease. These beneficial effects are completely abolished in Nrf2-/- mice, whereas the NAS is reduced by 52.9% in Nrf2+/+ mice[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: SKH-1 hairless (female, 10-12 weeks old)[1]
Dosage: 0.03 μM; 0.1 μM; 0.3 μM
Administration: topical; every 24 h; 3 doses
Result: Elevated NQO1 specific activity 3.5-fold (0.03 μmol dose), 4.2-fold (0.1 μM dose), and 4.9-fold (0.3 μM dose) compared to control.
Elevated GST specific activity 1.3-fold (0.03 μmol dose), 1.5-fold (0.1 μM dose), and 1.5-fold (0.3 μM dose) compared to control.
Induced statistically significant enzyme activity increases.
Animal Model: SKH-1 hairless (10-12 weeks old)[1]
Dosage: 0.1 μM/3 g diet; 0.3 μM/3 g diet
Administration: oral; daily; 11 days
Result: Increased liver NQO1 activity 2.4-fold (0.1 μM dose) and 3.5-fold (0.3 μM dose); increased liver GST activity 2.4-fold (0.1 μM dose) and 3.7-fold (0.3 μM dose); increased liver GSTA1 protein levels 1.4-fold (0.1 μM dose) and 1.7-fold (0.3 μM dose); increased liver GSTM1 protein levels 1.6-fold (0.1 μM dose) and 1.9-fold (0.3 μM dose); increased liver GSTP1 protein levels 2.2-fold (0.1 μM dose) and 3.6-fold (0.3 μM dose).
Increased skin NQO1 activity 2.2-fold (0.1 μM dose) and 3.5-fold (0.3 μM dose); increased skin GST activity 1.3-fold (0.1 μM dose) and 2.0-fold (0.3 μM dose).
Increased stomach NQO1 activity 3.8-fold (0.1 μM dose) and 4.5-fold (0.3 μM dose); increased stomach GST activity 3.5-fold (0.1 μM dose) and 5.0-fold (0.3 μM dose); increased stomach GSTA1 protein levels 2.2-fold (0.1 μM dose) and 2.4-fold (0.3 μM dose); increased stomach GSTM1 protein levels 2.4-fold (0.1 μM dose) and 3.3-fold (0.3 μM dose); increased stomach GSTP1 protein levels 2.3-fold (0.1 μM dose) and 3.0-fold (0.3 μM dose).
Induced statistically significant enzyme activity and protein level increases.
Caused no observed toxicity.
Showed no changes in cerebral cortex cytoprotective enzyme activities or protein levels.
Animal Model: C57BL/6 (female, 6-12 weeks of age)[2]
Dosage: 10 μM/kg
Administration: p.o.; single dose
Result: Increased hepatic NAD(P)H:quinone oxidoreductase 1 (NQO1) specific enzyme activity 2.4-fold compared to vehicle-treated controls.
Increased cardiac NQO1 specific enzyme activity 1.5-fold compared to vehicle-treated controls.
Animal Model: SKH-1 hairless[2]
Dosage: 40 nM per animal
Administration: topical; twice weekly; ~30 weeks
Result: Dramatically reduced tumor multiplicity and burden compared to controls.
Animal Model: C57BL/6N (adult male, 20-26 g, LPS-induced inflammation-associated depression-like behavior)[3]
Dosage: 1 mg/kg; 3 mg/kg; 10 mg/kg
Administration: p.o.; single dose
Result: Attenuated LPS-induced increases in serum TNF-α levels in a dose-dependent manner, with the 10 mg/kg dose reaching statistical significance.
Did not alter spontaneous locomotion in LPS-treated mice at 10 mg/kg.
Significantly reduced LPS-induced increases in immobility time in the TST and FST at 10 mg/kg compared to LPS-only treated mice.
Did not affect immobility time in control mice when administered alone.
Animal Model: C57BL/6 wild-type (Nrf2+/+) (male, 8-10 weeks of age, fed sequential high-fat plus 55% fructose (HF55Fr) diet for 15 weeks followed by high-fat plus 30% fructose (HF30Fr) diet for 9 weeks to induce NASH and insulin resistance)[4]
Dosage: 5 nM/g body weight
Administration: p.o.; 3 times weekly; 6 weeks
Result: Enhanced glucose clearance during ITT and GTT, and reduced hepatic gluconeogenesis during PTT compared to vehicle controls.
Decreased post-intervention weight gain, fasted plasma insulin, plasma cholesterol, and plasma alanine aminotransferase activity relative to vehicle-treated HF-fed mice.
Decreased liver triglyceride and cholesterol levels, reduced mRNA expression of Adrp, increased hepatic mRNA for lipid catabolism genes (Acox2, Ces1g, Acot7, Ppara, Cpt1a, Scad), decreased expression of lipogenic transcription factors (Srebf1, Mlxipl, Lxra, Xbp1s) and their target lipid synthesis enzymes (Acaca, Acly, Fasn, Scd1, Dgat2, Lipin1, Mgpat), and increased mRNA for lipid export genes (Mttp, ApoB).
Reduced hepatic protein levels of Bip, phospho-Ire1α, Xbp1s, phospho-eIf2α, and Atf4, and decreased mRNA for Atf4 and Chop relative to vehicle controls.
Attenuated nuclear accumulation of NF-κB p65, p52, p50; increased IκBα protein; decreased phospho-IKKα/β and phospho-JNK; and reduced mRNA for proinflammatory genes (Cox2, Nos2, Il1β, Ifng, Tnfa, Mcp1, Elastase, Mpo) relative to vehicle controls.
Reduced cleavage of Parp, caspase-9, and caspase-3; increased Bcl-2 mRNA; and decreased mRNA for Tgfβ, Col1a1, and α-Sma relative to vehicle controls.
Decreased hepatic malondialdehyde and protein carbonyl levels, increased GSH/GSSG ratio, and induced mRNA for antioxidant Nrf2-target genes (Gclc, Gclm, Gpx2, Nqo1, Gstm1, Hmox1, Txn1, Txnrd1, Slc7a11, Cat, Prdx6) relative to vehicle controls.
Reduced NAFLD Activity Score (NAS) from 4.9 to 2.9, with significant decreases in hepatocyte ballooning and fibrosis relative to vehicle controls.
Animal Model: C57BL/6 wild-type (Nrf2+/+) and Nrf2-knockout (Nrf2-/-) (male, 8-10 weeks of age, fed high-fat plus 30% fructose (HF30Fr) diet for 10 weeks to induce NASH and insulin resistance)[4]
Dosage: 5 nM/g body weight
Administration: p.o.; 3 times weekly; 6 weeks
Result: Enhanced insulin sensitivity during ITT and reduced hepatic gluconeogenesis during PTT compared to vehicle controls in Nrf2+/+ mice.
Reduced weight gain relative to vehicle-treated HF-fed mice in Nrf2+/+ mice.
Decreased liver triglyceride and cholesterol levels, reduced mRNA expression of Adrp, suppressed expression of lipogenic transcription factors (Srebf1, Lxra, Xbp1s) and their target lipid synthesis enzymes, and increased mRNA for lipid export genes (Mttp, ApoB) relative to vehicle controls in Nrf2+/+ mice.
Reduced hepatic protein levels of phospho-Ire1α, Xbp1s, p58IPK, phospho-eIf2α, and Atf4 relative to vehicle controls in Nrf2+/+ mice.
Attenuated nuclear accumulation of NF-κB p65 and p50, and reduced mRNA for Cox2 and Nos2 relative to vehicle controls in Nrf2+/+ mice.
Decreased hepatic malondialdehyde and protein carbonyl levels, and increased GSH/GSSG ratio relative to vehicle controls in Nrf2+/+ mice.
Reduced NAFLD Activity Score (NAS) from 2.125 to 1.0, with decreased steatosis and fibrosis relative to vehicle controls in Nrf2+/+ mice.
Showed no improvement in glucose homeostasis, weight gain, liver steatosis, ER stress, inflammation, oxidative stress, or liver histology relative to vehicle controls in Nrf2-/- mice; did not reduce liver triglyceride/cholesterol levels, suppress lipogenic gene expression, or mitigate NAS in Nrf2-/- mice.
Molecular Weight

330.38

Formula

C21H18N2O2
CAS No.
SMILES

C#C[C@]12C([C@@]3([C@@](C(C)(C(C(C#N)=C3)=O)C)([H])CC1)C)=CC(C(C#N)=C2)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
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TBE 31 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

TBE 31936475-62-6TBE31TBE-31Keap1-Nrf2Quinone ReductaseGlutathione S-transferaseApoptosisTNF ReceptorGlutathione transferasesGSTsTumor Necrosis Factor ReceptorTNFRAREc32 cellsKeap1/Nrf2 pathwayARE-dependent gene expressionPC12 cellsSKH-1 hairless miceHepa1c1c7 cellsNrf2Keap1GST isoformsNQO1Inhibitorinhibitorinhibit

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