Aprotinin acetate salt

Names

[ Name ]:
Aprotinin acetate salt

[Synonym ]:
cas9004-04-0
Trypsin Inhibitor
MFCD00130541

Biological Activity

[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]

Chemical & Physical Properties

[ 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.

Safety Information

[ 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

Articles

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 ...

Related Compounds

The content on this webpage is sourced from various professional data sources. If you have any questions or concerns regarding the content, please feel free to contact service1@chemsrc.com.