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).
For research use only. We do not sell to patients.
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
Isotype
Human IgG1 kappa
Recommend Isotype Controls
Species Reactivity
Human
In Vitro
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. Further protocols information, click here.
In Vivo
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.
Gene ID
Accession
Target
Serpin E1/SERPINE1/PAI1
Conjugated
Unconjugated
Reconsititution
The product can be reconstituted/diluted with sterile PBS or saline.
Format
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Product Image
Application
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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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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How to Choose the Right Model Animal
Choosing the right model animal is a validity-driven decision in which the species, strain, sex, age, genetic background, disease-induction method, outcome measures, and welfare burden must match the scientific question rather than laboratory tradition or convenience. A model should be selected by judging face validity, construct validity, and predictive validity: whether it resembles the human phenotype, whether it reproduces relevant mechanisms, and whether results are likely to predict human biology or treatment response. Animal studies often fail to translate because of species differences, weak disease resemblance, poor experimental design, inadequate reporting, publication bias, and underuse of randomization, blinding, and sample-size justification. Unresolved questions include how to rank competing models objectively, how much human-disease complexity must be reproduced for a given objective, and when non-animal systems such as organoids, ex vivo tissue, or computational models
Purity & Documentation
References
[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)