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Chemical Compound Review

U-46619     (Z)-7-[(1R,4R,5S,6S)-5- [(E,3S)-3...

Synonyms: CHEMBL521784, BSPBio_001534, SureCN12272421, CHEBI:583940, BML1-G04, ...
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Disease relevance of U-46619


High impact information on U-46619


Chemical compound and disease context of U-46619


Biological context of U-46619

  • Multiple dosing with GR32191, 17.5 mg (equivalent to 0.25 mg/kg for a 70 kg subject), three times daily (three subjects) or every 12 hours (six subjects), resulted in a cumulative inhibitory effect on U-46619 platelet aggregation in the apparent absence of a build-up of plasma concentrations of GR32191 [16].
  • During U46619 infusion pulmonary vasodilation was maintained up to 1 hour without tolerance [17].
  • Bradykinin and its analogues did not inhibit ADP-, collagen-, U46619-, or SFLLRN-induced platelet activation or the ability of alpha-thrombin to cleave chromogenic substrates, clot fibrinogen, or block alpha-thrombin binding to platelets [18].
  • These findings were paralleled by a 52+/-5% (P<.05) increase in cell number at 48 hours after addition of both mitogens as compared with 24+/-5% with thrombin alone and no change with U 46619 alone [19].
  • Pretreatment of SMC with thrombin for 4 hours markedly increased U 46619-induced mitogen-activated protein kinase activity, indicating thrombin-induced upregulation of functional thromboxane receptors in SMC [19].

Anatomical context of U-46619

  • GTPase activity (a function of alpha-subunit) in platelet membranes was normal in resting state but was diminished compared with normal subjects on stimulation with thrombin, platelet-activating factor, or the thromboxane A2 analog U46619 [20].
  • Porcine coronary arteries were stimulated with either KCl or U46619 [21].
  • Vascular responses to the thromboxane analogue U46619 were measured in four separate experimental protocols: 1) The vascular responses were measured in the presence and absence of intact endothelium to examine the role of endothelium-derived vasodilators [22].
  • Addition of U46619 to confluent fura 2-loaded endothelial cells caused a concentration-dependent rise in intracellular [Ca2+]i, with agonist concentrations of 300 nM producing a maximal [Ca2+]i rise [23].
  • These results suggest that the effects of U46619 in increasing vascular smooth muscle cell calcium efflux are receptor mediated [24].

Associations of U-46619 with other chemical compounds


Gene context of U-46619

  • U46619-mediated ERK activation was inhibited by the TP antagonist [1S-[1alpha,2beta-(5Z)-3beta,4alpha-]]-7-[3-[[2-(phenylamino)carbonyl]hydrazine] methyl]-7-oxabicyclo[-2,2,1-]hept-2yl]-5-heptenoic acid (SQ29,548), and by the mitogen-activated protein kinase kinase inhibitor 2'-amino-3'-methoxyflavone (PD 98059) [30].
  • Previous observations had demonstrated a role for bFGF in the expression of U46619 actions on protein synthesis [31].
  • To determine which G-proteins are implicated in the U46619-induced IL-6 synthesis, the interfering mutants of Galpha(q), Galpha12, or Galpha13 by were overexpressed in 1321N1 cells adenoviral approach [32].
  • U46619 increased DNA and protein synthesis, cell number, IP formation, [Ca2+]i, and MAPK and MAPKK activities, with EC50 values close to its Kd value for the low-affinity binding site in VSMCs from SHR [33].
  • Our data show that NKB is a dilator of the fetal vasculature, causing a maximal 25.1 +/- 4.5% (mean +/- SEM; n = 5) decrease in fetal-side arterial hydrostatic pressure (5- microM NKB bolus; effective concentration in the circulation, 1.89 nM) after preconstriction with U-46619 [34].

Analytical, diagnostic and therapeutic context of U-46619

  • Inhaled nitric oxide (150 ppm for 3 minutes) reduced pulmonary perfusion pressure, elevated by a continuous infusion of U46619, by 35 +/- 7% (mean +/- SEM, n = 5) [35].
  • The vasoconstrictive response to U46619 was enhanced for the first 30 minutes of reperfusion and returned to normal within 60 minutes [36].
  • Intracoronary infusion of U46619 (0.01-1.0 microgram/min) produced a dose-dependent constriction of LAD [22].
  • The relaxing activity of the effluent was monitored in canine coronary artery rings without endothelium (bioassay tissue) half-maximally contracted with U46619 [37].
  • As shown by flow cytometry, a tail population that had a minimal increase in F-actin upon stimulation with ADP or U46619 also contained the platelets with the least forward and right angle light scattering, which are functions of platelet size and shape [38].


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  20. Platelet signal transduction defect with Galpha subunit dysfunction and diminished Galphaq in a patient with abnormal platelet responses. Gabbeta, J., Yang, X., Kowalska, M.A., Sun, L., Dhanasekaran, N., Rao, A.K. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
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