MEDI-579
MEDI-579 is a fully human monoclonal antibody against PAI-1, with a KD value of 6 pM for human PAI-1 and 105 pM for rat PAI-1. MEDI-579 restores renal plasmin activity and inhibits PAI-1-mediated intracellular signal transduction. MEDI-579 reduces albuminuria, glomerulosclerosis severity, TGF-β1 expression level, and phosphorylated Smad2 level induced in diabetic mice. MEDI-579 decreases the levels of active PAI-1 in plasma and kidneys, and increases plasma plasmin level in a mouse model of lupus nephritis. MEDI-579 can be used in research related to diabetic nephropathy and lupus nephritis. The recommended isotype control is human IgG1 kappa (HY-P99001).
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Help & FAQs
Actividad biológica
Human IgG1 kappa
Human
MEDI-579 inhibits endogenous PAI-1-mediated plasminogen activation induced by TGFβ1 stimulation in normal human lung fibroblasts (NHLFs) with an IC50 of 10.5 nM; it also inhibits endogenous PAI-1-mediated plasminogen activation induced by TGFβ1 stimulation in mouse lung fibroblasts (MLgs) with an IC50 of 1.3 nM[2].
MEDI-579 Fab (25 pM-6.25 nM) exhibits ultra-high affinity for recombinant human PAI-1 with a KD value of 6 pM, and high affinity for recombinant rat PAI-1 with a KD value of 105 pM, as measured by surface plasmon resonance[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MEDI-579 (1-10 mg/kg; i.p.; twice weekly for 5 weeks/single administration) dose-dependently reduces the levels of active PAI-1 in plasma and kidneys of lupus nephritis mouse models, increases plasma plasmin levels, and exerts a protective effect against proteinuria[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:db/db mice (male, diabetic, uninephrectomized); db/m mice (male, lean nondiabetic littermates)[1]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:i.p.; twice weekly; 4 weeks
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Result:Reduced albuminuria by 33.3% (1 mg/kg dose), with no significant reduction in glomerulosclerosis.
Reduced albuminuria by 56.7%, glomerular PAS-positive matrix protein deposition by 41.5%, renal mRNA expression of TGF-β1, PAI-1, collagen I, and fibronectin, and renal protein levels of TGF-β1, total collagen, and fibronectin (3 mg/kg dose).
Reduced albuminuria by 61.3%, glomerular PAS-positive matrix protein deposition by 41.8%, renal mRNA expression of TGF-β1, collagen I, and fibronectin, and renal protein levels of TGF-β1, total collagen, and fibronectin; reduced renal PAI-1 mRNA expression to a lesser extent than the 3 mg/kg dose (10 mg/kg dose).
Caused no significant changes in body weight, blood glucose, or HbA1C with any dose.
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Animal Model:NZBxNZW/F1 mice (adenovirus-interferon-alpha injected intravenously at 0.3×1010 viral particles on day 0)[2]
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Dosage:1 mg/kg (twice weekly dosing); 10 mg/kg (twice weekly dosing); 10 mg/kg (single dose)
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Administration:i.p.; twice weekly; 5 weeks; i.p.; single dose
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Result:Reduced plasma active PAI-1 levels and elevated plasma plasmin levels 48 h post single 10 mg/kg dose.
Provided dose-dependent protection from proteinuria with twice weekly dosing of 1 mg/kg or 10 mg/kg for 5 weeks.
Significantly reduced urinary total protein (normalized to creatinine) compared to antibody control at week 5 with 10 mg/kg twice weekly dosing.
Significantly reduced active PAI-1 levels in kidney homogenates compared to antibody control with 10 mg/kg twice weekly dosing.
Serpin E1/SERPINE1/PAI1
Unconjugated
The product can be reconstituted/diluted with sterile PBS or saline.
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Product Image
ELISA, FACS, Functional assay
Chemical Information
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Formulation
Please refer to the lot-specific COA for specific buffer information.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Gu C, et al. An additive effect of anti-PAI-1 antibody to ACE inhibitor on slowing the progression of diabetic kidney disease. Am J Physiol Renal Physiol. 2016 Nov 1;311(5):F852-F863. [Content Brief]
[2]. Vousden KA, et al. Discovery and characterisation of an antibody that selectively modulates the inhibitory activity of plasminogen activator inhibitor-1. Sci Rep. 2019;9(1):1605. Published 2019 Feb 7. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MEDI-579 Related Classifications
HY-P992410 Related Classifications
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