Aprotinin acetate salt

[Description]:

Aprotinin is a bovine pancreatic trypsin inhibitor (BPTI) inhibitor which inhibits trypsin and chymotrypsin with Kis of 0.06 pM and 9 nM, respectively.

[Related Catalog]:

Signaling Pathways >> Anti-infection >> Influenza Virus

Research Areas >> Cardiovascular Disease

Peptides

[Target]

Ki: 0.06 pM (Trypsin), 9 nM (Chymotrypsin)[1]

[In Vitro]

Aprotinin, a serine protease inhibitor isolated from bovine lung, is a complex protease inhibitor that is an antifibrinolytic, inhibits contact activation, and decreases the inflammatory response to cardiopulmonary bypass[2]. Aprotinin inhibits trypsin (bovine, Ki= 0.06 pM), chymotrypsin (bovine, Ki= 9 nM), plasmin (human, 0.23 nM)[1]. Aprotinin is also a competitive protein inhibitor of NOS activity. It inhibits NOS-I and NOS-II with Ki values of 50 μM and 78 μM, respectively[3]. Aprotinin significantly inhibits fibrinolysis with an IC50 of 0.16±0.05 μM[4].

[In Vivo]

High dose aprotinin can reduce blood loss and transfusion requirements associated with primary cardiac procedures such as coronary artery bypass graft (CABG) or heart valve replacement surgery[5]. Aprotinin inhibits thrombus formation in a dose-dependent manner. Aprotinin at a dose of 1.5 mg kg-1 (bolus) and 3 mg kg-1 h-1 infusion (maintenance infusion) causes a tendency towards a reduction in bleeding time. Aprotinin significantly reduces the bleeding time starting at a dose of 3 mg kg-1 bolus plus 6 mg kg-1 h-1 showing a reduction of approximately 84%±2.9%. At the highest dose of 5 mg kg-1 and 10 mg kg-1 h-1, the strongest effects are observed[4]. Aprotinin may affect tumor necrosis factor-alpha (TNF) levels. Soluble TNFRI levels are significantly increased following I/R in the aprotinin treated wild type mice and not detected in all TNFRInull mice[6].

[Animal admin]

Rats: Male Wistar rats (180-220 g) are used in the study. Aprotinin is dissolved in physiological saline. Aprotinin is administered by bolus injection followed by a maintenance infusion. The doses given are 1.5 mg kg-1 and 3 mg kg-1 h-1, 3mg kg-1 and 6 mg kg-1 h-1 up to 5 mg kg-1 and 10 mg kg-1 h-1. Plasma concentrations for the two agents are assessed by pharmacokinetic studies in rats[4]. Mice: An intact mouse model of ischemia/reperfusion (30 min-I/60 min-R) is used and left ventricular peak + dP/dt is measured in wild type mice (WT, C57BL/6; n=10), WT mice with aprotinin (4mL/kg; n=10), transgenic mice devoid of the TNFRI (TNFRInull; n=10), and TNFRInull with aprotinin (n=10)[6].

[References]

[1]. Fritz H, et al. Biochemistry and applications of aprotinin, the kallikrein inhibitor from bovine organs. Arzneimittelforschung. 1983;33(4):479-94.

[2]. Levy JH, et al. Efficacy and safety of aprotinin in cardiac surgery. Orthopedics. 2004 Jun;27(6 Suppl):s659-62.

[3]. Venturini G, et al. Aprotinin, the first competitive protein inhibitor of NOS activity.Biochem Biophys Res Commun. 1998 Aug 10;249(1):263-5

[4]. Sperzel M, et al. Evaluation of aprotinin and tranexamic acid in different in vitro and in vivo models of fibrinolysis, coagulation and thrombus formation. J Thromb Haemost. 2007 Oct;5(10):2113-8. Epub 2007 Jul 31.

[5]. Davis R, et al. Aprotinin. A review of its pharmacology and therapeutic efficacy in reducing blood loss associated withcardiac surgery. Drugs. 1995 Jun;49(6):954-83.

[6]. Sabbagh MJ, et al. Aprotinin exacerbates left ventricular dysfunction after ischemia/reperfusion in mice lacking tumor necrosis factor receptor I. J Cardiovasc Pharmacol. 2008 Oct;52(4):355-62.

[Related Small Molecules]

[ Molecular Formula ]:
C₂₈₄H₄₃₂N₈₄O₇₉S₇

[ Molecular Weight ]:
6511.83000

[ Exact Mass ]:
6507.00000

[ Appearance of Characters ]:
lyophilized powder | white

[ Storage condition ]:
2-8°C

[ Stability ]:
Stable. Incompatible with strong oxidizing agents.

[ Water Solubility ]:
glycerol: soluble3mg/mL, clear, colorless (equilibration buffer containing 5% glycerol) | Freely soluble in water and in aqueous buffers of low ionic strength.

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Hazard Codes ]:
Xn,Xi

[ Risk Phrases ]:
42/43-36/37/38-20/21/22

[ Safety Phrases ]:
22-45-36/37-36-26

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
1

[ RTECS ]:
YN5080000

[ HS Code ]:
35040000

Engineering of a Biomimetic Pericyte-Covered 3D Microvascular Network.

PLoS ONE 10 , e0133880, (2015)

Pericytes enveloping the endothelium play an important role in the physiology and pathology of microvessels, especially in vessel maturation and stabilization. However, our understanding of fundamenta...

SH2-PLA: a sensitive in-solution approach for quantification of modular domain binding by proximity ligation and real-time PCR.

BMC Biotechnol. 15 , 60, (2015)

There is a great interest in studying phosphotyrosine dependent protein-protein interactions in tyrosine kinase pathways that play a critical role in many aspects of cellular function. We previously e...

Functional microRNA library screening identifies the hypoxamir miR-24 as a potent regulator of smooth muscle cell proliferation and vascularization.

Antioxid. Redox Signal. 21(8) , 1167-76, (2014)

Smooth muscle cells (SMCs) are key components within the vasculature. Dependent on the stimulus, SMC can either be in a proliferative (synthetic) or differentiated state. Alterations of SMC phenotype ...

Names

Biological Activity

Chemical & Physical Properties

Safety Information

Articles

Related Compounds