PAI-1
PAI-1 is a serine protease inhibitor (SERPIN). PAI-1 binds to and irreversibly inhibits uPA, tPA and furin; it also interacts with vitronectin, α1-acid glycoprotein, CRT, TLR4, proteasome α-3 subunit, uPAR, LRP1, Integrin αvβ3 and thrombin. PAI-1 regulates fibrinolysis, extracellular matrix turnover, cell migration, angiogenesis, inflammatory response and tissue remodeling; it mediates epithelial-mesenchymal transition (EMT)/endothelial-mesenchymal transition (EndMT), apoptosis and thrombus stabilization. PAI-1 can be used in research related to sepsis, acute lung injury, cardiovascular diseases, tissue fibrosis, diabetic nephropathy, obstructive nephropathy and non-insulin-dependent diabetes mellitus.
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- CAS 番号: 139446-70-1
- 分子式: C27H47N9O9S
- 分子量:673.78
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
生物活性
|
uPA |
TPa |
uPAR |
LRP1 |
αvβ3 |
TLR4 |
CRT |
Mouse recombinant PAI-1 (0.01-1 μg/mL; 90 min) dose-dependently inhibits phagocytosis of viable PAI-1-/- mouse bone marrow neutrophils by mouse peritoneal macrophages, with 1 μg/mL PAI-1 reducing phagocytic index to wild-type levels[1].
Rabbit anti-PAI-1 antibodies (1 μg/mL; 90 min) significantly enhance phagocytosis of viable wild-type mouse bone marrow neutrophils by mouse peritoneal macrophages, a PAI-1-dependent effect[1].
Mouse recombinant PAI-1 (1 μg/mL; 90 min) inhibits the enhanced phagocytosis of viable wild-type mouse bone marrow neutrophils by mouse peritoneal macrophages induced by CD47 blockade[1].
Mouse recombinant PAI-1 (1 μg/mL) reduces elevated surface calreticulin levels on viable PAI-1-/- mouse bone marrow neutrophils to wild-type levels[1].
Mouse recombinant PAI-1 (1 μg/mL; 90 min) significantly inhibits phagocytosis of apoptotic wild-type mouse bone marrow neutrophils by mouse peritoneal macrophages[1].
Active human PAI-1 potently inhibits human tPA and uPA with second-order rate constants between 106 and 107 M-1 s-1 via a canonical serpin-mediated inhibitory mechanism[2].
PAI-1 controls collagen levels, a key profibrotic marker, in human keloid-derived skin fibroblasts, with overexpression increasing collagen accumulation and depletion reducing it[3].
PAI-1 (5 μg; 2 h at 4°C) and Guanidine hydrochloride (HY-B0178A)-activated PAI-1 (4 M; 2 h at 20°C pre-treatment) bind to Heparin (HY-17567)-Sepharose at pH 7.4, with non-activated PAI-1 exhibiting a sharper elution profile at higher Na+Cl− concentrations than activated PAI-1[5].
PAI-1 has binding to heparin-Sepharose competed by soluble heparin and low molecular weight heparin, with soluble heparin exhibiting ~10-fold higher affinity for PAI-1 than low molecular weight heparin, as indicated by IC50 values of 7.0 μM and 73 μM, respectively[5].
PAI-1 (5 nM; 1 h at 37°C) has heparin dose-dependently mediate inhibition of α-thrombin, with maximal inhibition at 1 unit/mL heparin and a corresponding second-order association rate constant of 1.0 × 105 M-1s-1[5].
PAI-1 (7 nM; 1 h at 37°C) has heparin dose-dependently promote the formation of SDS-stable complexes with human α-thrombin, with maximal complex formation occurring at 1 unit/mL heparin[5].
PAI-1 potently inhibits the enzymatic activity of free tPA, reducing its activity by 82% when used at equivalent molar amounts[9].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (8-10-week-old, age- and sex-matched)[1]
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Dosage:2 μg per injection
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Administration:intratracheal; preincubation with neutrophils prior to administration
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Result:Significantly reduced phagocytic index (percentage of alveolar macrophages containing at least one ingested neutrophil) compared to mouse albumin control (P < 0.01).
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
化学情報
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CAS 番号 139446-70-1
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分子量 673.78
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分子式 C27H47N9O9S
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配列
Ala-Arg-Met-Ala-Pro-Glu
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シーケンスの短縮
ARMAPE
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
[1]. Park YJ, et al. PAI-1 inhibits neutrophil efferocytosis. Proceedings of the National Academy of Sciences of the United States of America. 2008 Aug 19;105(33):11784-9. [Content Brief]
[2]. Sillen M, et al. Targeting PAI-1 in Cardiovascular Disease: Structural Insights Into PAI-1 Functionality and Inhibition. Frontiers in cardiovascular medicine. 2020;7:622473. [Content Brief]
[3]. Ghosh AK, et al. PAI-1 in tissue fibrosis. Journal of cellular physiology. 2012 Feb;227(2):493-507. [Content Brief]
[4]. Huang Y, Border WA, Yu L, Zhang J, Lawrence DA, Noble NA. A PAI-1 mutant, PAI-1R, slows progression of diabetic nephropathy. J Am Soc Nephrol. 2008 Feb;19(2):329-38. [Content Brief]
[5]. Ehrlich HJ, et al. Functional interaction of plasminogen activator inhibitor type 1 (PAI-1) and heparin. Biochemistry. 1991 Jan 29;30(4):1021-8. [Content Brief]
[6]. Oda T, et al. PAI-1 deficiency attenuates the fibrogenic response to ureteral obstruction. Kidney international. 2001 Aug;60(2):587-96. [Content Brief]
[7]. Matsuo S, et al. Multifunctionality of PAI-1 in fibrogenesis: evidence from obstructive nephropathy in PAI-1-overexpressing mice. Kidney Int. 2005 Jun;67(6):2221-38. [Content Brief]
[8]. Vaughan DE. PAI-1 and atherothrombosis. J Thromb Haemost. 2005 Aug;3(8):1879-83. [Content Brief]
[9]. Tang Z, et al. Surface immobilization of a protease through an inhibitor-derived affinity ligand: a bioactive surface with defensive properties against an inhibitor. Chemical communications (Cambridge, England). 2015 Sep 28;51(75):14263-6. [Content Brief]
[10]. Nordt TK, et al. Induction of plasminogen activator inhibitor type-1 (PAI-1) by proinsulin and insulin in vivo. Circulation. 1995 Feb 01;91(3):764-70. [Content Brief]
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)