TAK-442, a Direct Factor Xa Inhibitor, Inhibits Monocyte Chemoattractant Protein 1 Production in Endothelial Cells via Involvement of Protease-Activated Receptor 1.

Oral blood coagulation inhibitors and their receptors, such as factor Xa (FXa), thrombin, and the thrombin receptor protease-activated receptor 1 (PAR1), are entered into clinical trials for acute coronary syndrome therapy; however, the results obtained so far are different for each drug. The underlying mechanisms of the results have not been fully investigated. We studied the anti-inflammatory effects of the selective FXa inhibitor TAK-442 on human endothelial cells, with comparing those of the selective thrombin inhibitor melagatran and the PAR1 antagonist vorapaxar.

Anti-thrombotic effect of a factor Xa inhibitor TAK-442 in a rabbit model of arteriovenous shunt thrombosis stimulated with tissue factor.

Objective: Arterial thrombosis is triggered by tissue factor, which is a transmembrane glycoprotein can be released into the blood circulation after plaque rupture. Animal models with reflecting ruptured plaque lesions will be useful to understand efficacy of anticoagulant. In this study, we sought to improve a common arteriovenous shunt model in rabbits, aiming for a model of thrombosis stimulated with tissue factor, and to investigate the anti-thrombotic effect of a direct factor Xa inhibitor TAK-442 in the model.

Antidyslipidemic potential of a novel farnesoid X receptor antagonist in a hamster model of dyslipidemia: Comparative studies of other nonstatin agents.

We attempted to clarify the therapeutic capability of antagonists of the farnesoid X receptor (FXR), a nuclear receptor that regulates lipid and bile acid metabolism. Herein, we report the antidyslipidemic effects of a novel synthesized FXR antagonist, compound-T1, utilizing a dyslipidemic hamster model. Compound-T1 selectively inhibited chenodeoxycholic acid-induced FXR activation (IC , 2.

Combinational effects of farnesoid X receptor antagonist and statin on plasma lipid levels and low-density lipoprotein clearance in guinea pigs.

Aims: We previously reported anti-dyslipidemic effects of a farnesoid X receptor antagonist in monkeys. In this study, we compared the cholesterol-lowering effects of single and combined administration of a farnesoid X receptor antagonist, compound-T8, and the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor atorvastatin in a guinea pig model.

Main Methods: Plasma levels of 7α-hydroxy-4-cholesten-3-one, a marker of hepatic cholesterol 7α-hydroxylase activity, were measured after a single administration of compound-T8.