Thromboxane A2, as an unstable intermediate between the prostaglandin endoperoxides and thromboxane B2, is a potent inducer of platelet aggregation and causes vasoconstriction.
15(R)-Pinane thromboxane A2 is the (R)-epimer of pinane thromboxane A2 . 15(R)-PTA2 does not inhibit collagen-induced platelet aggregation (IC50s = 120-130 μM). It does not affect gastric tone in isolated rat gastric fundus when used at concentrations of 0.5 or 1.5 μg/ml and is less effective than PTA2 at inhibiting prostaglandin-induced contraction of isolated rat stomach muscle.
8-iso-15-keto Prostaglandin F2α (8-iso-15-keto PGF2α) is a metabolite of the isoprostane 8-iso PGF2α in rabbits, monkeys, and humans. 8-isoprostane (8-iso PGF2α) is a prostaglandin-like product of non-specific lipid peroxidation. In both humans and monkeys, exogenously infused 8-iso PGF2α is converted primarily to metabolites having 2 or 4 carbon atoms removed from the top side chain by β-oxidation. A similar pattern is observed when tritiated 8-iso PGF2α is infused into rabbits. Early in the infusion (within 1-2 minutes) 8-iso -15-keto PGF2α was a major component of the metabolite profile, which was comprised mostly of unmetabolized 8-iso PGF2α. 8-iso -15-keto PGF2α is a vasoconstrictor when tested on the rat isolated thoracic aorta, acting via the TP (thromboxane) receptor.
RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 uM) and shows no effect on PAR-2, PAR-3, or PAR-4. RWJ-56110 dihydrochloride inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), quite selective relative to U46619 . RWJ-56110 dihydrochloride blocks angiogenesis and blocks the formation of new vessels in vivo. RWJ-56110 dihydrochloride induces cell apoptosis[1][2].
Proteinase-activated receptors (PARs) are a family of G protein-coupled receptors activated by the proteolytic cleavage of their N-terminal extracellular domain, exposing a new amino terminal sequence that functions as a tethered ligand to activate the receptors.RWJ56110 inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM) while being quite selective relative to collagen and the thromboxane mimetic U46619 [1].RWJ-56110 dihydrochloride is fully inhibits thrombin-induced RASMC proliferation with an IC50 value of 3.5 μM. RWJ-56110 dihydrochloride shows blockade of thrombin's action with RASMC calcium mobilization (IC50=0.12 μM), as well as with HMVEC (IC50=0.13 μM) and HASMC calcium mobilization (IC50=0.17 μM)[1].RWJ56110 (0.1-10 μM; 24-96 hours) inhibits endothelial cell growth dose-dependently, with half-maximal inhibitory concentration of RWJ56110 is approximately 10 μM[2].RWJ56110 (0.1-10 μM; 6 hours) inhibits DNA synthesis of endothelial cells in a thymidine incorporation assays. Endothelial cells are in fast-growing state (50-60% confluence), RWJ56110 inhibits cell DNA synthesis in a dose-dependent manner, but when cells that are in the quiescent state (100% confluent), the inhibitory effect of PAR-1 antagonists is much less pronounced[2].RWJ56110 (0.1-10 μM; pretreatment for 15 min) inhibits thrombin-induced Erk1/2 activation in a concentration-dependent manner. However, when endothelial cells are stimulated by FBS (final concentration 4%), it reduces partially the activated levels of Erk1/2[2].RWJ56110 (30 μM; 24 hours) has an inhibitory effect on endothelial cell cycle progression. It reduces the percentage of cells in the S phase, while alterations in the percentages of G1 and G2/M cells are less pronounced[2]. Western Blot Analysis[2] Cell Line: Endothelial cells
[1]. Andrade-Gordon, et al.Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor. oc Natl Acad Sci U S A. 1999 Oct 26;96(22):12257-62. [2]. Panagiota Zania, et al. Blockade of angiogenesis by small molecule antagonists to protease-activated receptor-1: association with endothelial cell growth suppression and induction of apoptosis. J Pharmacol Exp Ther. 2006 Jul;318(1):246-54.
1,2,3-Trilinoelaidoyl-rac-glycerol is a triacylglycerol that contains linoelaidic acid at the sn-1, sn-2, and sn-3 positions. Dietary administration of 1,2,3-trilinoelaidoyl-rac-glycerol (0.6-6.3% w/w) lowers serum levels of thromboxane B2 , prostaglandin F2 (PGF2), and PGE in rats.1
|1. Bruckner, G., Goswami, S., and Kinsella, J.E. Dietary trilinoelaidate: Effects on organ fatty acid composition, prostanoid biosynthesis and platelet function in rats. J. Nutr. 114(1), 58-67 (1984).
E 3040 is a dual inhibitor of 5-lipoxygenase and thromboxane A(2) synthetase. It is involved with eicosanoid production. E 3040 also has anti-inflammatory properties.