NBE5
NBE5 is an orally active hydrophobic tag-targeting (Hyt) degrader (HyTTD) that targets Keap1. NBE5 mimics protein misfolding and recruits the molecular chaperone Hsp90, while achieving targeted degradation of Keap1 through both the ubiquitin-proteasome system and the autophagy-lysosome system. Consequently, NBE5 relieves the inhibition of the transcription factor Nrf2 by Keap1, potently activates the Nrf2-mediated endogenous antioxidant pathway, and upregulates the expression of downstream antioxidant proteins such as HO-1 and GCLM. NBE5 effectively alleviates oxidative stress and inflammatory damage, and exhibits excellent in vivo activity in a mouse model of acute colitis induced by DSS (HY-116282C).
NBE5 consists of a hydrophobic tag (HY-W022007), a Keap1-Nrf2 ligand (HY-14909), and a linker (HY-W014831).
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- Fòrmula: C50H73N3O4
- Peso molecular:780.13
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Help & FAQs
Actividad biológica
NBE5 consists of a hydrophobic tag (HY-W022007), a Keap1-Nrf2 ligand (HY-14909), and a linker (HY-W014831).
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HSP90 |
NBE5 (1.0 μM; 12 h) induces potent Keap1 degradation in HCT116, RKO, and BEAS-2B cells, with the highest activity (92.5% degradation) observed in BEAS-2B cells[1].
NBE5 (0.1-10.0 μM; 12 h) induces concentration-dependent Keap1 degradation in HCT116 and RKO cells over 12 h, with higher potency (lower DC50, higher Dmax) in HCT116 cells[1].
NBE5 (1.0 μM; 1.5-24 h) induces time-dependent Keap1 degradation in HCT116 and RKO cells, with faster degradation kinetics (shorter DT50) observed in HCT116 cells[1].
NBE5 (2.0 μM; 6-18 h, plus washout culture) mediates Keap1 degradation in HCT116 and RKO cells that depends on both the ubiquitin-proteasome system and autophagy-lysosome system, involves enhanced Keap1-Hsp90 interaction, and produces sustained degradation after washout[1].
NBE5 (0.5-2.5 μM; 12 h) activates the Nrf2 pathway in HCT116, RKO, and BEAS-2B cells via Keap1 degradation, leading to increased nuclear Nrf2, upregulated downstream antioxidant enzyme protein and mRNA levels, with no effect on Keap1 transcription[1].
NBE5 (2.0 μM; 12 h) selectively induces Keap1 degradation in HCT116 cells, activates the Nrf2 antioxidant pathway, upregulates autophagy-related and HSP70 family proteins, and shows no significant effect on off-target proteins IKKβ and SLC30A1[1].
The DC50 values of NBE5 for Keap1 degradation in HCT116 and RKO cells were 0.82 μM and 1.72 μM, respectively; furthermore, at a concentration of 1 μM, the maximum degradation rate of Keap1 in BEAS-2B cells reached 92.5%[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCT116 and RKO cell
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Concentration:2.0 μM
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Incubation Time:6-18 h
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Result:Mediated Keap1 degradation, increased nuclear Nrf2, upregulated downstream antioxidant enzyme protein.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male)[1]
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Dosage:5 mg/kg; 20 mg/kg
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Administration:p.o.; once daily; 10 days
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Result:Reduced weight loss compared to DSS-only treated mice.
Increased colon length compared to DSS-only treated mice.
Lowered Disease Activity Index scores compared to DSS-only treated mice.
Significantly reduced Keap1 intensity in colon tissues compared to DSS-only treated mice.
Potently decreased colonic inflammation and reversed histopathological changes of the colon compared to DSS-only treated mice.
Chemical Information
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Peso molecular 780.13
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Fòrmula C50H73N3O4
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SMILES
O=C(NCC1C(C2)C=CC2C1)CCCCCCCCCCNC([C@](CC3)(CCC(C)(C4)C)[C@]4([H])[C@](C(C=C5[C@]6(CC[C@]7([H])[C@@]5(C=C(C(C7(C)C)=O)C#N)C)C)=O)([H])[C@@]36C)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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