2. Metabolic Enzyme/Protease TGF-beta/Smad Stem Cell/Wnt
  3. PAI-1 TGF-beta/Smad
  4. 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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MEDI-579

MEDI-579 Chemical Structure

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MEDI-579 Related Antibodies

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Description

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)[1][2].

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.

MEDI-579 Related Antibodies
In Vivo

MEDI-579 (1-10 mg/kg, i.p., twice weekly for 4 weeks) reduces albuminuria by 56.7% and glomerular matrix deposition by 41.5% in uninephrectomized diabetic db/db mice[1].
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.

Animal Model: db/db mice (male, diabetic, uninephrectomized); db/m mice (male, lean nondiabetic littermates)[1]
Dosage: 1 mg/kg; 3 mg/kg; 10 mg/kg
Administration: i.p.; twice weekly; 4 weeks
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.
Animal Model: NZBxNZW/F1 mice (adenovirus-interferon-alpha injected intravenously at 0.3×1010 viral particles on day 0)[2]
Dosage: 1 mg/kg (twice weekly dosing); 10 mg/kg (twice weekly dosing); 10 mg/kg (single dose)
Administration: i.p.; twice weekly; 5 weeks; i.p.; single dose
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

5054  [NCBI]

Accession
Target

Serpin E1/SERPINE1/PAI1
Application

ELISA, FACS, Functional assay
Conjugated

Unconjugated
Reconsititution

The product can be reconstituted/diluted with sterile PBS or saline.
Formulation

Please refer to the lot-specific COA for specific buffer information.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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MEDI-579 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:

MEDI-579MEDI579MEDI 579PAI-1TGF-beta/SmadPlasminogen activator inhibitor-1Transforming growth factor betaNHLFsmouse lung fibroblastsMLgsplasminogen activator inhibitor type 1lupus nephritisdiabetic nephropathyrenal plasminvitronectinnormal human lung fibroblastsInhibitorinhibitorinhibit

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