Glutoborin
Glutoborin is an orally active GLUT1-specific proteasome inhibitor with a Kd value of 119 nM for GLUT1. Glutoborin binds to GLUT1, inhibits proteasome activity, restricts IκBα degradation, blocks NF-κB activation, and inhibits GLUT1-mediated glucose transport to elevate blood glucose levels. Glutoborin inhibits pro-inflammatory gene expression, B cell activation, autoantibody production and macrophage function, disrupts the interaction between macrophages and B cells, and alleviates systemic inflammation, neuroinflammation and blood-brain barrier damage. Glutoborin can be used in research related to cerebral malaria.
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- Formel: C34H44BCl2N5O4
- Molecular Weight:668.46
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
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Biologische Aktivität
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GLUT1 119 nM (Kd) |
Glutoborin (0.049-6.25 μM; association time 0s, dissociation time 60s) binds purified GLUT1 protein with a dissociation constant KD of 119 nM[1].
Glutoborin exhibits high binding affinity for GLUT1, as demonstrated by a docking score of -12.52 in in silico assays[2].
Glutoborin (100 nM; 3 hours) potently inhibits proteasome activity in HEK293T cells[1].
Glutoborin (100 nM; 3 h wild-type, 30 min transfected 24 h prior) selectively inhibits proteasome activity in GLUT1-expressing HEK293T cells, with enhanced inhibition in cells expressing the membrane-localized GLUT1S226D mutant[2].
Glutoborin (49-6250 nM; 30 minutes) inhibits proteasome activity in a GLUT1-dependent manner, as GLUT1-knockdown 4T1 cells are resistant to its effects while wild-type 4T1 cells show concentration-dependent inhibition[1].
Glutoborin (20 nM; 12 hours post 12-hour LPS/IFNγ stimulation) inhibits proteasome activity and reduces Tnf expression in LPS/IFNγ-stimulated RAW264.7 macrophages[1].
Glutoborin (20 nM; 12 h) suppresses pro-inflammatory gene (Tnf, Il6) expression in LPS/IFN-γ-stimulated RAW264.7 macrophages[2].
Glutoborin (2-hour pretreatment, followed by 30-minute LPS/IFNγ stimulation) limits IκBα degradation by restricting proteasome activity, thereby suppressing downstream NF-κB activation in RAW264.7 macrophages[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RAW264.7 macrophages (LPS/IFN-γ-stimulated)
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Concentration:20 nM
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Incubation Time:12 h (following 12 h of LPS/IFN-γ stimulation)
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Result:Markedly suppressed the expression of the pro-inflammatory genes *Tnf* and *Il6* in activated RAW264.7 macrophages.
Glutoborin (10 mg/kg; i.v.; 3 doses (days 2, 4, 6 post-infection)) treatment confers 100% survival in Plasmodium berghei ANKA-infected mice, while suppressing pathogenic B cell activation, autoantibody production, and systemic and neuroinflammation[2].
Glutoborin (10 mg/kg; i.v.; 3 doses (days 0, 2, 4)) exhibits superior in vivo safety in healthy mice[2].
Glutoborin (1-10 mg/kg; i.v., p.o.; single dose) demonstrates broad tissue distribution, rapid absorption, and moderate clearance in healthy male Sprague-Dawley rats following single intravenous (1 mg/kg) or oral (10 mg/kg) administration[2].
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, 6-8 weeks old, Plasmodium berghei ANKA infection)[1]
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Dosage:10 mg/kg
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Administration:administered on days 2, 4, and 6 post-infection
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Result:Conferred 100% survival.
Maintained platelet counts within normal physiological ranges.
Reduced blood-brain barrier disruption measured by Evans blue dye extravasation OD620.
Decreased cerebral hemorrhagic area.
Lowered brain expression of pro-inflammatory genes Cxcl10, Isg15, and Tnf.
Significantly reduced serum total IgM levels on days 4, 5, and 6 post-infection.
Significantly reduced anti-platelet IgM levels on day 7 post-infection.
Ameliorated splenomegaly.
Reduced the frequency and absolute number of splenic Ly6c+Ccr2+ macrophages.
Decreased the proportion of activated splenic B cells.
Suppressed gene programs associated with vesicle-mediated exocytosis and IFN-I signaling in macrophages.
Reduced Isg15 and Ifit2 expression in sorted splenic Ly6c+Ccr2+ macrophages.
Reduced hepatic and cardiac toxicity.
Promoted more rapid weight recovery compared to bortezomib-treated controls.
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Animal Model:C57BL/6J (male, 6-8 weeks old, cerebral malaria model via intraperitoneal injection of 1 × 104 Plasmodium berghei ANKA-infected red blood cells)[2]
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Dosage:10 mg/kg
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Administration:i.v.; 3 doses (days 2, 4, 6 post-infection)
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Result:Conferred 100% survival of infected mice.
Maintained platelet counts within normal physiological parameters.
Significantly reduced blood-brain barrier disruption (measured by decreased Evans blue extravasation).
Lowered expression of pro-inflammatory genes Cxcl10, Isg15, and Tnf in brain tissue.
Reduced peripheral parasitemia.
Restored normoglycemia.
Ameliorated splenomegaly.
Suppressed expansion of marginal zone B cells.
Lowered CD19+CD69+ activated B cell percentages.
Reduced total serum IgM and anti-platelet IgM levels.
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Animal Model:C57BL/6J (male, 6-8 weeks old)[2]
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Dosage:10 mg/kg
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Administration:i.v.; 3 doses (days 0, 2, 4)
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Result:Showed significantly lower liver and cardiac toxicity compared to bortezomib-treated controls.
Enabled rapid weight recovery to baseline levels.
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Animal Model:Sprague-Dawley (male)[2]
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Dosage:1 mg/kg (i.v.); 10 mg/kg (p.o.)
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Administration:i.v.; single dose; p.o.; single dose
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Result:Achieved an initial plasma concentration above 100 ng/mL, which declined to approximately 2 ng/mL at 24 hours following intravenous administration of 1 mg/kg.
Reached an initial plasma concentration around 50 ng/mL, which declined to approximately 1 ng/mL at 24 hours following oral administration of 10 mg/kg.
Chemical Information
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Molecular Weight 668.46
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Formel C34H44BCl2N5O4
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SMILES
CC(C)C[C@@H](B(O)O)NC(CN1C(C2=CC=CC=C2)=CC(C3=CC(OCCN(CC4)CCN4C5=CC=CC=C5)=CC=C3)=N1)=O.Cl.Cl
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
Glutoborin Related Classifications
HY-187165 Related Classifications
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