u46619

U-46619是一种有效的TXA2激动剂，是一种血栓素A2类似物（内过氧化物），有诱导肌球蛋白轻链9 (Myl9)基因缺失小鼠主动脉平滑肌(SM)收缩的功能。

MNS 是一种酪氨酸激酶抑制剂和广谱抗血小板药物，是一种 β-硝基苯乙烯衍生物。它完全抑制 U46619 (IC50:2.1 μM)、ADP (IC50:4.1 μM)、花生四烯酸 (IC50:5.8 μM)、胶原 (IC50:7.0 μM)和凝血酶 (IC50:12.7 μM)诱导的血小板聚集，并抑制 Src (IC50:27.3 μM)、Syk (IC50:2.8 μM) 和 FAK (IC50:97.6 μM)。

(±)12-HEPE is produced by non-enzymatic oxidation of EPA. It contains equal amounts of 12(S)-HEPE and 12(R)-HEPE. The biological activity of (±)12-HEPE is likely mediated by one of the individual isomers, most commonly the 12(S) isomer in mammalian systems. 12-HEPE inhibits platelet aggregation with the same potency as 12-HETE, exhibiting IC50 values of 24 and 25 µM, respectively. [1] These compounds are also equipotent as inhibitors of U46619-induced contraction of rat aorta (IC50s = 8.6-8.8 µM).[2]

Epoxyeicosatrienoic acids (EETs), such as 11(12)-EET and 14(15)-EET, are cytochrome P450 metabolites of arachidonic acid that have been identified as endothelium-derived hyperpolarizing factors with vasodilator activity. 14,15-EE-5(Z)-E is a structural analog of 14,15-epoxyeicosatrienoic acids (14,15-EET) that antagonizes EET-induced relaxation of vascular smooth muscle. Relaxation of U46619-constricted bovine arteries by 14,15-EET could be inhibited approximately 80% by 14,15-EE-5(Z)-E at a concentration of 10 μM. 14,15-EE-5(Z)-E does not appear to antagonize nitric oxide- or iloprost-mediated vascular relaxation.

TPα and TPβ are two isoforms of the human TP receptor, the G protein-coupled receptor (GPCR) that mediates the actions of thromboxane A2 (TXA2). Although their distinct physiological functions have not been fully elucidated, TPβ is believed to be responsible for vascular endothelial growth factor-induced endothelial cell differentiation and migration whereas TPα appears to be the predominant isoform expressed in platelets. CAY10535 is a TP receptor antagonist that shows ~20-fold selectivity for TPβ (IC50 = 99 nM) relative to TPα (IC50 = 1,970 nM) in the inhibition of U46619-mediated Ca2+ mobilization. This compound exhibits relatively poor activity on platelets (IC50 = 985 nM) when inhibiting U-46619-induced platelet aggregation.

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.

Sp-5,6-DCl-cBIMPS 为一种高效特异的 cAMP 依赖性蛋白激酶(cAMP-PK)激活剂，能够促进胰岛素释放，并抑制U46619引起的血小板Rho、Gq及G12 G13的激活[3]。

2-Deacetoxytaxinine B is a strongly inhibitor against U46619-induced aggregation, it shows strong inhibitory effects against arachidonic acid (AA)-induced aggregation.

Cirsiumaldehyde 是一种从Lobelia chinensis、Cornus officinalis 成熟果实和 Hippophae rhamnoides 果实中分分离出的化合物。Cirsiumaldehyde 在胶原蛋白存在下对 U46619 诱导（1~5 uM）的大鼠血小板聚集的抑制浓度为 0.8~1.0 ug mL。