The inhibition of thrombin and chymotrypsin by heparin-cofactor II

Strub, Dietrich; Storck, Josef; Zimmermann, R. E.

doi:10.1016/0049-3848(92)90126-u

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…Prolyl endopeptidase inhibitor is linked to phosphodiesterase III inhibitor. Chymotrypsin inhibitor is strongly linked to 5 HT antagonist, VCAM-1 antagonist, carbacephem, and thrombin inhibitor (experimental information exists to support the last two relationships , ). Moreover, factor VIIa inhibitor is linked to factor Xa inhibitor (in fact, the factor VII enzyme is activated to factor VIIa by different proteases, among which are thrombin factor IIa, and factor Xa).…”

Section: Resultsmentioning

confidence: 99%

Detecting Drug Promiscuity Using Gaussian Ensemble Screening

Pérez‐Nueno

Venkatraman

Mavridis

et al. 2012

J. Chem. Inf. Model.

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Polypharmacology describes the binding of a ligand to multiple protein targets (a promiscuous ligand) or multiple diverse ligands binding to a given target (a promiscuous target). Pharmaceutical companies are discovering increasing numbers of both promiscuous drugs and drug targets. Hence, polypharmacology is now recognized as an important aspect of drug design. Here, we describe a new and fast way to predict polypharmacological relationships between drug classes quantitatively, which we call Gaussian Ensemble Screening (GES). This approach represents a cluster of molecules with similar spherical harmonic surface shapes as a Gaussian distribution with respect to a selected center molecule. Calculating the Gaussian overlap between pairs of such clusters allows the similarity between drug classes to be calculated analytically without requiring thousands of bootstrap comparisons, as in current promiscuity prediction approaches. We find that such cluster similarity scores also follow a Gaussian distribution. Hence, a cluster similarity score may be transformed into a probability value, or "p-value", in order to quantify the relationships between drug classes. We present results obtained when using the GES approach to predict relationships between drug classes in a subset of the MDL Drug Data Report (MDDR) database. Our results indicate that GES is a useful way to study polypharmacology relationships, and it could provide a novel way to propose new targets for drug repositioning.

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Section: Resultsmentioning

confidence: 99%

Detecting Drug Promiscuity Using Gaussian Ensemble Screening

Pérez‐Nueno

Venkatraman

Mavridis

et al. 2012

J. Chem. Inf. Model.

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“…HCII, a serpin with a 25% overall-and a 50% reactive site homology to ATIII (41), is secreted by the liver into blood where it is present at a concentration of about 1.2 p,M. HCII only inhibits thrombin in coagulation (42). Analogous to ATIII, its inhibitory activity is dramatically enhanced in the presence of GAG.…”

Section: Heparin Cofactor II (Hcii)mentioning

confidence: 99%

Anticoagulant Properties of the Vascular Endothelium

1997

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“…The ability of AT to inhibit serine proteases is markedly enhanced in the presence of heparin or heparin sulfate [17]. Apart from inhibitory effect of heparin on the coagulation cascade, heparin alone or in the complex with either AT or heparin cofactor II also inhibits the activity of trypsin [19,20] and chymotrypsin [20], as well as prevents the transformation of inactive trypsinogen to active trypsin [21,22].…”

Section: Introductionmentioning

confidence: 99%

Pretreatment with Warfarin Attenuates the Development of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

et al. 2020

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In acute pancreatitis (AP), pancreatic damage leads to local vascular injury, manifesting as endothelial damage and activation, increased vascular permeability, leukocyte rolling, sticking and transmigration to pancreatic tissue as well as activation of coagulation. Previous studies have shown that pretreatment with heparin or acenocoumarol inhibits the development of AP. The aim of the present study was to check the impact of pretreatment with warfarin, an oral vitamin K antagonist, on the development of ischemia/reperfusion-induced AP in rats. AP was induced by pancreatic ischemia followed by reperfusion of the gland. Warfarin (90, 180 or 270 µg/kg/dose) or vehicle were administered intragastrically once a day for 7 days before induction of AP. The effect of warfarin on the severity of AP was assessed 6 h after pancreatic reperfusion. The assessment included histological, functional, and biochemical analyses. Pretreatment with warfarin given at a dose of 90 or 180 µg/kg/dose increased the international normalized ratio and reduced morphological signs of pancreatic damage such as pancreatic edema, vacuolization of acinar cells, necrosis and the number of hemorrhages. These effects were accompanied by an improvement of pancreatic blood flow and a decrease in serum level amylase, lipase, pro-inflammatory interleukin-1β and plasma level of D-dimer. In contrast, pretreatment with warfarin given at a dose of 270 µg/kg/dose led to an increase in severity of pancreatic damage and biochemical indicators of AP. In addition, this dose of warfarin resulted in deaths in some animals. Pretreatment with low doses of warfarin inhibits the development of AP induced by pancreatic ischemia followed by reperfusion.

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The inhibition of thrombin and chymotrypsin by heparin-cofactor II

Cited by 7 publications

References 22 publications

Detecting Drug Promiscuity Using Gaussian Ensemble Screening

Detecting Drug Promiscuity Using Gaussian Ensemble Screening

Anticoagulant Properties of the Vascular Endothelium

Pretreatment with Warfarin Attenuates the Development of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

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